Medicago and GlaxoSmithKline (GSK) have started Phase III clinical testing of Medicago’s plant-derived COVID-19 vaccine candidate in combination with GSK’s pandemic adjuvant, as part of the ongoing Phase II/III study. Medicago received approval from Canadian and US regulatory authorities to proceed with enrolment of healthy adults in the Phase III portion of the trial based on positive interim Phase II results.

Medicago’s plant-derived vaccine candidate against COVID-19 uses Coronavirus-Like-Particle (CoVLP) technology with the vaccine composed of recombinant spike (S) glycoprotein expressed as virus-like-particles (VLPs) co-administered with GSK’s pandemic adjuvant. Two doses of 3.75μg of CoVLP are administered 21 days apart.

The vaccine candidate, in combination with the pandemic adjuvant, was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) on 17 February 2021. Fast Track designation allows the FDA to expedite the development and review of new medicines and vaccines intended to treat or prevent serious conditions and address an unmet medical need.

The Phase II portion of the trial is approaching completion and results are expected to be made publicly available in April 2021.

Takashi Nagao, CEO and President of Medicago said: “We are pleased to take the significant step of initiating the Phase III clinical trial at sites around the world. This brings us one step closer to delivering an important new COVID-19 vaccine and contributing to the global fight against the pandemic along with our partner GSK.”

Thomas Breuer, Chief Medical Officer, GSK Vaccines said, “This advance to late-stage clinical testing further reinforces our confidence in the adjuvanted vaccine candidate’s potential to make a difference in the continued fight against COVID-19. We look forward to sharing results later this year.”

Carolyn Finkle, Chief Operating Officer of Medicago said: “The FDA’s decision to grant Fast Track designation for Medicago’s vaccine candidate will help us expedite our efforts to bring the first plant-derived COVID-19 vaccine to market, subject to regulatory approval. We are grateful to the FDA and look forward to continuing to work with them as we move forward in our clinical trials, planned application for Emergency Use Authorisation and eventual vaccine licensure application process.”

Source: Pharmafield

바이오앱, 식물 단백질 활용 의약품 개발 기업 한미사이언스와 코로나19 그린백신 개발 나서 현재 동물실험 단계, 후보물질서 높은 항체 반응 확인 올해 하반기 기술특례로 코스닥 상장 목표

코스닥 상장을 추진 중인 바이오앱이 코로나19 그린백신 개발에 본격 나서고있다. 식물에서 추출한 단백질을 활용하는 다소 생소한 방식이다. 하지만 정부 및 국내 기업들이 손을 내밀 정도로 가능성을 인정받고 있어 하반기 상장을 위한 움직임이 가시화 될 전망이다.

9일 업계에 따르면 바이오앱은 최근 한미사이언스(008930), 포스텍과 공동으로 코로나19 그린백신 대량생산 공정 개발에 돌입했다. 이번 사업은 질병관리청 국립보건연구원으로부터 지원받아 진행된다. 바이오앱은 화이자와 모더나의 mRNA 기술 기반 단백질 발현물질을 식물(담뱃잎) 단백질 재조합 기술로 후보물질을 개발했다. 한미사이언스와 공동으로 코로나 그린백신을 개발 중이다.

포스텍 연구교수 출신 손은주 대표가 이끄는 바이오앱은 식물에서 추출한 유전자 및 단백질로 바이오 의약품을 개발 생산하는 바이오벤처다. 식물 기반 단백질유전공학 기술을 활용한 ▲단백질 고발현 ▲단백질 분리정제 ▲분자면역 증강제 ▲그린나노 기술이 핵심이다. 담뱃잎을 활용한 돼지열병 마커백신 ‘허바백’을 세계 최초로 개발해 가능성을 인정받았고, 인체용 바이오 의약품 개발을 위해 크리스퍼 유전자가위 기술을 보유하고 있는 툴젠의 기술을 도입하는 등 사업 확대에도 나서고 있다.

◇한미가 먼저 러브콜, 미래 가능성에 투자

그린백신 가능성에 주목한 한미사이언스는 바이오앱에 먼저 손을 내밀었다. 업계에 따르면 한미 측은 그린백신 등 그린바이오 산업에 관심이 있었고, GSK가 캐나다 메디카고의 기술로 코로나 그린백신 개발에 나서면서 확신을 가진 것 알려졌다. 업계 관계자는 “한미 측은 포스텍으로부터 바이오앱을 소개받아 회사를 방문했고, 이후 가능성을 확인하고 코로나 그린백신 개발을 위한 MOU와 지분투자가 단행됐다”고 말했다.

실제 한미사이언스는 지난해 6월 바이오앱과 코로나 그린백신 공동개발 협약을 맺었고, 2달 뒤 45억원을 투자해 바이오앱 지분 5.46%를 취득했다. 한미사이언스는 동물실험을 직접 진행해 담배에서 생산한 코로나 그린백신 후보 단백질의 높은 항체 반응을 확인했다. 바이오앱 관계자는 “코로나 그린백신 제품 대량생산 공정 개발 및 시설 구축을 통해 연내 임상시험 신청을 할 것”이라고 설명했다.

그린백신은 식물에서 분리 정제한 재조합 단백질을 활용해 기존 백신 대비 부작용이 거의 없고 효과는 우수하다는 게 장점으로 꼽힌다. 메디카고는 GSK와 담뱃잎을 활용해 코로나 재조합 단백질 백신을 개발 중이다. 캐나다 정부와는 7600만 도스 백신 공급계약을 체결했다. 우리 정부도 지난해 9월 각종 지원을 통해 식물백신, 유전자가위, 생명소재, 동물용 의약품 등 그린바이오 산업을 2030년까지 12조원 규모로 키운다는 계획을 발표한바 있다.

그린백신 등 그린바이오 산업에 대한 가능성을 먼저 인지한 투자업계도 바이오앱에 선제 투자를 진행했다. 바이오앱은 2017년 포스코기술투자, 대교인베스트먼트, 디티앤인베스트먼트 등이 참여한 시리즈A에서 40억원을 유치했고, 2018년 시리즈B 에서는 포스코, 대교 등 기존 기관투자자와 CKD창업투자 등 신규 투자자들이 50억원을 추가 투자했다. 지난해에는 시리즈C 투자로 75억원을 유치했다. 특히 포스코기술투자는 2012년부터 지속적인 투자를 진행했다.

박세영 포스텍기술투자 심사역은 “식물을 활용해 백신을 생산하는 방식이 새로웠다. 해당 기술이 플랫폼으로 자리 잡게 된다면 파급력이 상당할 것으로 봤다”며 “미래 사업 발굴이라는 측면에서 큰 의미가 있다고 판단했다”고 말했다.

◇“코스닥 상장 하반기 추진”

바이오앱은 지난해 기술특례상장을 시도했지만 기술성평가에 가로막혔다. 사업성 부분에서 낮은 평가를 받았다는 게 회사 측 설명이다. 하지만 바이오앱은 올해 한미사이언스와 코로나 그린백신 임상 1상에 돌입할 계획이고, 그 시기에 맞춰 다시 한번 기술특례 상장을 노린다는 계획이다.

바이오앱은 한미 측과 코로나 그린백신 외에도 동물용 의약품을 중심으로 한 중국 사업도 추진 중이다. 한미사이언스와는 국내에서 인체용 바이오의약품 개발을 진행하고, 한미 측 중국 자회사와는 중국에서 돼지열병 백신 등 동물용 의약품 중심 사업을 진행한다는 계획이다. 회사 측은 코로나 그린백신 임상 진행과 중국 쪽 사업이 진척되면 상장에도 긍정적인 영향을 끼칠 것으로 내다봤다.

손대현 바이오앱 본부장은 “작년 기술특례상장을 추진했지만, 사업성에서 낮은 평가를 받으면서 기술성평가 문턱을 넘지 못했다”면서 “올해 다시 기술특례 방식으로 코스닥 상장을 추진하고 있다. 상장 추진 시기는 코로나 그린백신 임상이 진행되는 하반기 정도가 될 것”이라고 말했다.

출처: 이데일리

식물 생명 공학 기술을 활용한 글로벌 바이오 제약 회사 바이오앱이 한미사이언스(008930), 포스텍과 공동으로 ‘코로나19 그린백신 대량생산 공정 개발’에 돌입한다고 8일 밝혔다.

바이오앱은 지난 2월9일 질병관리청 국립보건연구원에서 실시한 ‘코로나19 백신개발을 위한 용역사업 공모’에 선정됐다. 이번 용역 사업 수주를 통해 바이오앱은 정부에서 연구개발비를 지원받아 한미사이언스, 포스텍과 공동으로 코로나19 그린백신 대량생산 공정 개발을 진행할 예정이다.

그린백신은 식물을 생산플랫폼으로 활용하여 생산되는 재조합단백질 백신으로, 안전성과 신속성, 경제성이 뛰어나 최근 미국과 캐나다 등에서 감염병 대응을 위한 최적의 기술로 각광받고 있다.

캐나다 소재 메디카고사에서는 담배(니코티아나 벤타미아나)에서 코로나19 재조합단백질 백신을 생산해 임상 2/3상을 진행 중이며, 캐나다 정부와 7600만도스의 백신 공급계약을 체결했다. 또한 미국의 캔터키 바이오프로세싱사도 코로나19 그린백신 임상 1상을 진행하고 있다.

국내에서는 바이오앱과 포스텍 연구진이 코로나19 그린백신 개발을 주도하고 있으며, 전임상 단계임에도 불구하고 담배에서 생산한 코로나19 그린백신 후보단백질의 동물실험에서 높은 항체 반응을 확인했다.

손은주 바이오앱 대표이사는 “코로나19 그린백신 제품 대량생산을 위한 생산 공정 개발 및 시설 구축을 통해 코로나19 그린백신의 연내 임상시험 신청을 목표로 하고 있다”며 “국내 바이오벤처기업의 원천기술과 바이오제약 그룹의 제조, 임상기술 간의 오픈이노베이션 협력이 우수한 성과로 창출될 수 있도록 함께 노력하겠다”고 전했다.

한편, 바이오앱은 기술특례를 통한 코스닥 상장을 추진하고 있다.

출처: 이데일리

Hydrangea is a popular decorative plant because of its blue and lavender-colored flowers. It belongs to the Hydrangeaceae family.

Its root and rhizome — or underground stem — have been used traditionally as herbal medicine to treat urinary conditions.

However, you may wonder what science has to say about its acclaimed benefits and safety.

This article explores hydrangea root’s benefits, uses, supplements, side effects, and dosage.

What is hydrangea root?

The genus Hydrangea is made up of over 70 plant species that belong to the Hydrangeaceae family

Out of these, Hydrangea paniculata, Hydrangea macrophylla, and Hydrangea arborescens are the most popular when it comes to medicinal properties.

H. paniculata and H. macrophylla are native to Asia, while H. arborescens is native to the eastern United States.

Other common names for these species include hortensia, seven bark, wild hydrangea, smooth hydrangea, bigleaf hydrangea, and mophead hydrangea.

Hydrangea root is a supplement made from these plant’s roots and underground stems, also known as the rhizomes.

The supplement has been used in folk medicine for hundreds of years to treat prostate and bladder infections due to its purported diuretic effects — meaning its ability to increase urine output. However, no available scientific evidence backs up this claim.

It’s also speculated that it might help treat kidney and bladder stones and enlarged prostate.

Hydrangea root is a supplement made from various hydrangea plants. It’s traditionally used to treat urinary tract infections and stones.

Potential benefits

Test-tube and animal studies suggest that some hydrangea root compounds may provide medicinal benefits.

May protect your kidneys

Elevated levels of certain blood markers are associated with kidney injury. Studies in mice indicate that hydrangea extract may lower some of these markers.

For example, high levels of blood urea nitrogen (BUN) indicate kidney damage. Studies in animals with medically induced kidney injury found that hydrangea extract significantly reduced BUN levels.

One of these studies also observed less kidney damage in mice treated with the extract, compared with a control group.

Another study similarly found that skimmin, an active molecule found in hydrangea extract, reduced BUN, blood creatinine, and urinary albumin excretion (UAE) in mice with kidney inflammation. High creatinine and UAE levels also indicate kidney dysfunction.

What’s more, research in mice determined that the extract improved medicinally induced kidney injury by downregulating kidney inflammation and cell death, although the effect was only observed in cases of previously damaged kidneys.

Still, despite these promising results, human studies are needed.

May have anti-inflammatory properties

Hydrangea root is rich in a compound called coumarin. Both coumarin and its derivative skimmin may offer anti-inflammatory properties.

Inflammation can lead to increased levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), nitric oxide (NO), and interleukin 6 (IL-6) — all of which are known as pro-inflammatory markers.

Animal research suggests that both coumarin and skimmin may inhibit NO production and IL-6 activation and suppress the upregulation of TNF-α and IL-1β.

Additionally, in one study in mice hydrangea root extract inhibited the infiltration of inflammatory cells like macrophages and neutrophils into kidney tissue, which suggests another potential anti-inflammatory mechanism.

Lastly, in addition to coumarin and skimmin, the extract contains loganin and sweroside, two compounds known for their anti-inflammatory activities.

All this being said, keep in mind that research in humans is lacking.

May have antioxidant effects

If there are too many reactive oxygen species (ROS) in your body, a phenomenon called oxidative stress can occur, which can lead to tissue damage and other detrimental health effects.

Thankfully, molecules known as antioxidants protect against oxidative stress and said damage.

Coumarins in hydrangea root have antioxidant properties. For example, a mouse study found that hydrangea extract significantly reduced oxidative stress, suggesting potent antioxidant effects.

Similarly, another study determined that the extract significantly lowered oxidative stress markers such as NO and malondialdehyde (MDA) in mice.

It’s important to note that these benefits have not been confirmed in research in humans.

Other potential benefits

While research in humans is lacking, it’s speculated that hydrangea root may also:

Lower blood sugar levels. Test-tube studies and animal research indicate that the compound skimmin in hydrangea root may relieve insulin resistance and enhance blood sugar uptake.

Protect your liver. Test-tube research has found multiple compounds in hydrangea stems that may protect from liver toxicity.

Provide cancer-fighting properties. One test-tube study determined that hydrangenol, another compound present in hydrangeas, may inhibit bladder cancer cell reproduction and spread.

Hydrangea root may protect from kidney damage and provide antioxidant and anti-inflammatory effects, among other benefits. However, keep in mind that research in humans is needed.

Potential side effects

There’s little research on hydrangea root side effects and toxicity.

Anecdotally, user reports have described potential side effects like chest tightness, upset stomach, nausea, vomiting, and dizziness.

Also, according to an older study from 2000, the compound hydrangenol — an allergen in hydrangeas — may cause allergic reactions when hydrangea root comes in direct contact with the skin.

Lastly, due to the lack of information regarding the toxicity of the root, people who are pregnant or breastfeeding should avoid its use.

Make sure to consult your healthcare provider before consuming hydrangea root supplements.

There’s little research regarding hydrangea root toxicity. However, anecdotally reported side effects include nausea, upset stomach, dizziness, chest tightness, and vomiting.

Forms, uses, and dosage

You may find hydrangea root supplements online in capsule, tincture, powder, syrup, and liquid extract forms.

Dried or powdered hydrangea root is often made into tea, prepared by simmering 1 tablespoon (15 grams) of the supplement in an 8-ounce (250-mL) cup of water.

Due to the lack of research in humans, there’s currently no dosage recommendation for hydrangea root supplements.

However, doses higher than 2 grams have been linked to the previously mentioned side effects.

You may find hydrangea root in powder, tincture, syrup, and capsule form. There’s currently no established dosage for the supplement, though it’s speculated that taking over 2 grams could cause unwanted side effects.

The bottom line

Hydrangea root has been used for hundreds of years to treat urinary conditions like prostate and bladder infections, enlarged prostate, and kidney and bladder stones.

However, test-tube and animal research only back up its use as a possible way to protect your kidneys from injury. Additionally, it’s speculated that some of its plant compounds may provide anti-inflammatory and antioxidant activities.

It’s important to note that human research on all of its purported benefits is lacking. This also means that there’s no established dosage for the supplement, and its use may cause side effects such as nausea, vomiting, upset stomach, and dizziness.

You may find hydrangea root supplements in various forms, including capsules, tinctures, powder, syrup, and liquid extracts.

Source: healthline

Samara Polytech chemists investigated the potential anticarcinogenic effects of extracts obtained from plant materials of lingonberry, raspberry, black chokeberry, grapes, Krasnodar green tea, ginseng, fireweed and coffee, and also evaluated their effect on the growth and viability of colon cancer cells. The research was carried out within the framework of the state assignment for fundamental research No. 0778-2020-0005, its results were published Dec. 29, 2020 in the journal Proceedings of Universities. Applied Chemistry and Biotechnology (DOI: https://doi.org/10.21285/2227-2925-2020-10-4-613-626).

Prevention is the most cost-effective and long-term strategy for controlling this disease. It is now well known that almost 50% of all malignant tumors can be prevented with proper nutrition based on natural products with a preventive effect.

"Polyphenols are the largest variety of plant components. It is this class of chemical compounds that have shown powerful antioxidant properties. They actively fight against cellular damage caused by free radicals, slowing down the aging and preventing oxidation. In addition, they protect the body from inflammatory, cardiovascular, neurodegenerative diseases, and some forms of cancer", one of the authors of this study, associate professor of the Department of Technology and Organization of Public Catering of Samara Polytech Natalya Eremeeva explains. "We studied in detail the beneficial properties of lingonberry, raspberry, black chokeberry, grapes, Krasnodar green tea, ginseng, fireweed and coffee.

When conducting the MTT cytotoxicity test, the scientists found that the ginseng extract was the most cytotoxic, and the coffee extract was the least cytotoxic. It has been proven that all the studied extracts are able to reduce the expression of pro-inflammatory genes. The most pronounced inhibitory effect on the expression of these genes is possessed by the extracts of chokeberry and fireweed.

The research team supposes that this study may serve as a basis for conducting in vivo experiments to determine anticarcinogenic activity.

For reference:

MTT test is a colorimetric test to assess the metabolic activity of cells.

Cytotoxicity is the ability of chemicals to damage tissue cells, including malignant tumors.

Samara Polytech as a flagship university offers a wide range of education and research programs and aims at development and transfer of high-quality and practically-oriented knowledge. The university has an established reputation in technical developments and focuses on quality education, scientific and pragmatic research, combining theory and practice in the leading regional businesses and enterprises. Education is conducted in 30 integrated groups of specialties and areas of training (about 200 degree programs including bachelor, master programs and 55 PhD programs) such as oil and gas, chemistry and petrochemistry, mechanics and energy, transportation, food production, defense, IT, mechanical and automotive engineering, engineering systems administration and automation, material science and metallurgy, biotechnology, industrial ecology, architecture, civil engineering and design, etc.

Source: EurekAlert!

Ireland-based biopharmaceutical company Jazz Pharmaceuticals announced the biggest acquisition in the cannabis space to date after it agreed to buy the global leader in developing cannabinoid-based medicines, GW Pharmaceuticals for $7.2 billion last week.

Ireland-based biopharmaceutical company Jazz Pharmaceuticals announced the biggest acquisition in the cannabis space to date after it agreed to buy the global leader in developing cannabinoid-based medicines, GW Pharmaceuticals for $7.2 billion last week.

Following this announcement, GW Pharmaceuticals shares, which rose over 10% in 2020, jumped 49% to a record high of $217.5 on Wednesday. On the other hand, Jazz Pharmaceuticals shares seen its biggest intraday volatility since August 2015.

According to the agreement, Jazz to acquire GW for $220.00 per American Depositary Share (ADS), in the form of $200.00 in cash and $20.00 in Jazz ordinary shares, for a total consideration of $7.2 billion, or $6.7 billion net of GW cash. The deal is expected to close in the second quarter of 2021.

“Cannabis has the potential to cause significant disruption to the traditional medical market, and as more Pharma companies get involved, such as Jazz, we expect to see continued innovation and product development,” said Owen Bennett, equity analyst at Jefferies.

“Second, it raises the possibility of more M&A, with other big Pharma bidding for cannabis companies. Here we would be careful assuming most cannabis players could be subject to an offer.”

GW Pharma‘s Epidiolex, the first plant-derived cannabinoid medicine ever approved by the U.S. Food and Drug Administration, registered sales of over $500 million for the U.K.-based company in 2020. Market experts forecasts sales to hit $1 billion over the coming months, Reuters reported.

Source: FX EMPIRE

Novavax’s COVID-19 vaccine is able to offer protection against COVID-19 according to results of a phase three clinical trial released by the manufacturers of the vaccine.

According to a statement released by Novavax, results from the U.K branch of the study show that the vaccine is 89.3 percent effective in offering protection against the virus.

In a study that was involved 15,000 participants aged 18 to 84years in the UK and South Africa, the vaccine candidate was shown to be 95.6% effective against the original strain of coronavirus, and 85.6% effective against the variant first detected in the UK.

When it was tested in South Africa among HIV-negative participants, the vaccine showed to be 60 percent effective. When tested on persons living with HIV, the vaccine offered 49 percent protection.

Studies in the U.S and Brazil are still ongoing.

The vaccine is a combination of an engineered protein from the virus and a plant based ingredient which helps the body generate a stronger immune response to the virus. If the body encounters the virus after vaccination, the immune system should be able to fight off the virus.

For the virus to be effective, two jabs of the vaccine are needed three weeks (21 days) part. It will be mass produced for COVAX by the Serum Institute of India. Uganda signed up for the COVAX facility and has ordered for two million doeses. Dr Alfred Driwale the Uganda National Expanded Programme on Immunization programme manager says they do not know when the vaccine will be delivered.

“There are very many vaccine candidates under the COVAX facility. Right now we do not know what vaccine we shall be allocated or what quantities we shall get. But we are expecting a decision soon,” he said.

According to the health ministry, Uganda has ordered for 18 million doses of COVID-19 vaccines.

The Novavax vaccine, called NVX-CoV2373, is the seventh vaccine candidate that has proven to be effective against COVID-19, after the Pfizer, Moderna, Astrazena, Johnson & Johnsons, Russia’s Sputnik V COVID-19 and China’s Sinopharm vaccines.

The vaccine can be stored at fridge temperature just like the Astrazeneca vaccine. In terms of cost, it is estimated that each jab will cost an equivalent of USD 16.

Source: The Independent

Researchers in Greece have demonstrated the antiviral effects of Cretan aromatic plant oils on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent responsible for coronavirus disease 2019 (COVID-19).

The team showed that a combination of essential oils from Mediterranean thyme (Thymbra capitata L. Cav.), Greek sage (Salvia fruticosa Mill.), and Cretan dittany (Origanum dictamnus L.), exhibited remarkable antiviral activity against SARC-CoV-2 in Vero E6 cells.

Furthermore, in a proof-of-concept study involving patients with mild COVID-19, administration of the essential oil mixture significantly improved both general and local symptoms.

The study was conducted by researchers from the University of Crete in Heraklion, the Democritus University of Thrace in Alexandroupolis, and University General Hospital in Alexandroupolis.

Elias Castanas and colleagues propose that if the findings are validated in clinical trials, the essential oil mix (called CAPeo) could provide a novel, inexpensive option for the treatment of mild COVID-19.

A pre-print version of the research paper is available on the medRxiv* server, while the article undergoes peer review.

An unmet need for effective therapies

Since the COVID-19 outbreak began in Wuhan, China, in late 2019, unprecedented efforts have been made to develop effective vaccines and therapies to protect against and treat SARS-CoV-2 infection.

Safe and effective vaccines have now started to emerge and various therapeutics are at different stages of preclinical and clinical development.

However, Castanas and colleagues say that although there are some effective therapies for hospitalized patients in intensive care units, the need for inexpensive, safe, and effective treatments for non-critically-ill patients outside of the hospital setting remains unmet.

“Accordingly, drug repurposing for candidates acting against known or predicted SARS-CoV-2 protein actions has been advanced, while natural products have also been tested,” writes the team.

Previous studies of CAPeo

Castanas and colleagues recently proved that CAPeo was effective at reducing the severity and duration of upper respiratory tract viral infections in humans. In vitro studies of influenza and human rhinovirus 14 (HRV14) also demonstrated that treatment with CAPeo inhibited the nuclear translocation of viral nucleoproteins and disrupted the transcription of viral proteins.

Furthermore, the researchers have already reported the safety of administering CAPeo (1 ml/day of 1.5% CAPeo in extra virgin olive oil) in both humans and animals.

“Here, we suggest CAPeo as a potential novel agent, for the safe and effective therapeutic management of mild ambulatory cases of COVID-19,” they say. “It presents remarkable antiviral properties against Influenza A and B strains and HRV14, while it is safe in both experimental animals and humans.”

What did the researchers do?

Now, the team has extended the previous studies to SARS-CoV-2 and assayed the effects of CAPeo on Vero E6 cells infected with the virus.

The researchers also performed a proof-of-concept study involving 17 patients with PCR-confirmed SARS-CoV-2 and mild COVID-19.

What did they find?

The study found that CAPeo exerted significant antiviral activity against SARS-CoV-2 in Vero E6 cells at concentrations similar to those the researchers previously reported.

CAPeo reduced viral release into the culture medium by more than 80%. This effect (albeit around 35% smaller) persisted when CAPeo concentrations were reduced to 1% of the suggested dose for humans.

Interestingly, a prophylactic effect was also observed when Vero E6 cells were incubated with different concentrations of CAPeo 2 hours prior to infection.

“CAPeo, in addition to a possible therapeutic action, might be dotted with a prophylactic effect against SARS-CoV-2 virus,” writes the team.

The proof-of-concept study

Encouraged by the results, Castanas and colleagues next performed a proof-of-concept intervention involving 17 SARS-CoV-2-positive patients with mild symptoms of COVID-19.

The severity and duration of general and local symptoms among the participants were assessed for 14 days.

“We have chosen this interval as previous studies report a self-resolution of mild COVID-19 cases in 14 or 14-21 days and the persistence of the virus in upper respiratory tract samples for about ten days,” explain the researchers.

Since the study did not include a control group, the team compared the evolution of disease symptoms among the participants against those reported in previous studies of non-hospitalized patients.

What were the results?

The administration of 1 mL per day of 1.5% CAPeo in olive oil significantly improved general and local symptoms among the participants by the end of the study.

At the beginning of the study, the main general symptoms included headache, myalgia, weakness, and fever, in accordance with previous reports, says the team.

However, compared with other study findings, fever was low (less than 37.5°C) in all but one patient.

The frequency of other symptoms (including gastrointestinal, respiratory and ear nose and throat [ENT]) was also low, and the severity mild.

The study also found that significant general symptoms of COVID-19 – namely headache, fatigue, fever –entirely resolved. In contrast, previous studies found that headache and fatigue (but not fever) persisted at 14 days and beyond, says the team.

Furthermore, the majority of both general and local symptoms had almost completely resolved by the end of the first week.

The authors recommend that CAPeo is tested in clinical trials

The researchers say the findings suggest that CAPeo possesses potent antiviral and prophylactic activity against SARS-CoV-2.

“We suggest that CAPeo, pending additional confirmation of results through a prospective randomized controlled trial, may represent a valuable addition for the prevention and therapeutic management of mild COVID-19 ambulatory patients,” concludes the team.

Source: News Medical

Research to make medicines capable of fighting COVID-19, from frankincense trees in Oman, is being jointly undertaken by the University of Nizwa and the University of Oxford.

The project is looking to isolate certain key compounds from frankincense – known for its healing properties – and to use them to make antibiotics.

The resin contains large numbers of naturally-occurring chemicals that could be used to inhibit the ability of the COVID-19 virus to infect people.

“We realised that the properties of these compounds being anti-inflammatory can be very beneficial, because we could use these to inhibit the m-protease protein in the COVID virus,” explained Dr Ahmed Sulaiman Al Harrasi, the Vice Chancellor for Research and Graduate Studies at the University of Nizwa.

“This protein is present in the spike protein of the virus, which is used to enter the host cells, such as the lungs, in the case of humans.

“We ran models of the m-protease, in which we treated this with our active drugs,” he added. “We could see a very strong binding between the two, which means the inhibition of the virus by these compounds could be very strong.”

The project is led by Dr Al Harrasi, who also serves as the Chair of the Natural and Medical Sciences Research Centre, which he helped found, and is conducting this research, and Dr Christopher Schofield, the Head of Organic Chemistry at Oxford.

“It starts with the isolation of active ingredients from the frankincense resin,” explained Al Harrasi.

“It then has to go through several procedures conducted here. Some of these are self-developed methodologies and protocols that helped us isolate these bio-active components, purify them, and then characterise them.

“We came to know their structure through different spectroscopic techniques such as nuclear resonance, X-rays and mass spectrometry,” he added.

“Various techniques are used to identify and elucidate the structure of those components used to make drugs isolated from frankincense.”

The resin was chosen for this research as it contains a high number of boswellic acids, which are known to be excellent anti-inflammatory components, which have been used to treat ailments such as diabetes, cancer, joint pain and Crohn’s disease.

“Some of these are about to reach pharmacy shelves as real drugs,” added Al Harrasi, who added that the next step of this research will involve testing the quality and strength of the compounds isolated from frankincense. “Oxford’s labs, in this regard, are one of the best established facilities in the world.

“There are other plants that contain various alkaloids – some of these are very similar to chloroquine, one of the drugs used to treat COVID-19,” he explained. “At some stage, this drug was withdrawn and then brought back. The advantages of the alkaloids we have isolated is that they are naturally occurring, their structures are fascinating, and they are very promising.

“We are testing them with our colleagues at Oxford,” he went on to say. “One of these potential plants is haplophyllum tuberculatum, a very well-known plant for traditional medicine in Oman. We have a bank of more than 1,000 compounds – some of them are isolated from different plants of Oman, while others are synthetically modified by us.

“We have studied more than 70 medicinal plants of Oman,” Al Harrasi said. “The NMSRC is also working on various other activities – marine species, micro-organisms, bacteria, fungi, biomedical research, anti-venoms, anti-diabetes and anti-cancer research. We have finished phase one here, and now we are in phase two. Phase three remains.

“If things go well, maybe in a year’s time, we will execute the project with regard to the 20 active components regarding COVID-19 and the m-protease enzyme,” he revealed. “We have 12 research labs, and we have managed to establish a large network of active collaborators, and have large numbers of specialised equipment,” Collaboration for research projects such as this one has been established with different stakeholders including the Ministry of Agriculture, Fisheries and Water Resources, Ministry of Health, Oman Botanic Garden, the Office for the Conversation of Environment, Sultan Qaboos University, Ministry of Higher Education, Research and Innovation, and several others. Internationally, the university is collaborating with more than 50 institutes around the world.

Source: Times of Oman

한미사이언스(대표이사 임종윤)와 바이오앱(대표이사 손은주)이 현재 COVID-19 통합 백신과 치료용 물질의 빠른 개발과 임상, 대량 생산 생태계 구축을 위한 '광속 사업 개발 프로젝트'를 빠르게 진행하고 있다.

지난 22일 한미사이언스는 그린백신 개발 바이오 벤처기업인 바이오앱과의 공동연구를 통하여 식물바이러스 나노 테크놀로지를 접목한 코로나19 백신 후보물질의 전자현미경 VLP(Virus Like Particle)을 공개하였다.

이번에 전임상에 돌입한 후보물질은 최근 FDA로부터 긴급사용승인을 획득한 화이자와 모더나社의 mRNA 기술 기반의 단백질 발현물질을 식물을 통한 단백질 재조합(Protein Recombinant) 기술을 활용하여 개발한 신약으로, 순수 국내 자체 기술로 개발하는데 큰 의미를 두고 있다. 양사는 이 기술이 산업 과학 분야의 국가적 자산으로서의 가치가 충분하다는 기대를 갖고 있다.

양사는 이미 동물모델 실험을 통하여 코로나19 그린백신 후보물질이 완치 환자보다 높은 중화항체를 형성할 수 있다는 사실을 확인한 바 있으며, 현재 독성실험 등 백신 허가를 위한 전임상 단계를 진행 중이다. 또한 최근에 강력한 전염력으로 문제가 되고 있는 영국형 변종 바이러스를 타깃하는 후보 물질로서 Covid-19 그린백신의 실증사업을 신청 중에 있다고 밝혔다.

한미사이언스와 바이오앱 양사는 2021년 내에 가장 안전한 코로나 그린백신 임상시험 착수를 목표로, 그린백신 생산에 필요한 공정테스트를 진행하고 있다. 코로나19 상용 생산을 위해서 이와는 별도로 한미 바이오 플랜트에서는 바이오앱에서 개발한 그린백신 정제기술을 상용화 수준까지 높이는 공정을 테스트 중이고, 긴급 생산에 대비해 소규모 생산과 실증산업을 동시에 진행할 수 있는 생산시설을 설계 중이다. 이 결과에 따라 신속한 스케일업을 계획하고 있다.

한미사이언스는 지난 6월 바이오앱과 그린백신 개발 및 사업화를 위한 업무협약을 체결한 이후 최근 바이오앱에 대한 전략적 지분투자를 진행하였다고 밝혔다. 이는 양사간의 구체적 연구 협력을 통해 코로나19 그린백신 공동 개발에 속도를 내겠다는 의지로 분석된다.

출처: 메디파나 뉴스

BAT’s US Biotech arm, Kentucky BioProcessing (KBP) today announced plans to commence a Phase I first-time-in-human study of its COVID-19 vaccine candidate following approval of its Investigational New Drug application by the U.S. Food and Drug Administration (FDA). Enrolment for the study is expected to begin shortly.

The COVID-19 vaccine candidate (KBP-COVID-19; NCT04473690) will become one of a number of potential vaccines to have progressed beyond pre-clinical testing. The study is designed to enroll a total of 180 healthy volunteers who will be divided into two age cohorts, age 18-49 and age 50-70. Each group will then be subdivided into low and high dose treatment groups (N~45) and randomised 2:1 to receive either the low dose (15 μg KBP-COVID-19 vaccine + 0.5 mg adjuvant) or placebo, or high dose (45 μg KBP-COVID-19 vaccine + 0.5 mg adjuvant) or placebo. Results from the study are expected mid-2021 and, if positive, would allow for continued progress into a Phase 2 study, subject to regulatory approval.

The candidate vaccine has been developed using KBP’s innovative fast-growing plant-based technology. This unique approach has a number of possible advantages, including the rapid production of the vaccine’s active ingredients in around 6-weeks, compared to several months using conventional methods. The candidate vaccine also has the potential to be stable at room temperature, which could be a significant advantage for healthcare systems and public health networks worldwide. If successful, the speed of production of the active ingredients has the potential to reduce the time between identifying new viruses and strains, and vaccine development and deployment to those who need it.

KBP is conducting and recently completed enrolment for a Phase I clinical study of its quadrivalent (four-strain) influenza vaccine candidate (KBP-V001; NCT04439695), which uses the same nicotiana benthamiana plant-based technology platform.

Dr David O’Reilly, BAT’s Director of Scientific Research said:

“Moving into human trials with both our COVID-19 and seasonal flu vaccine candidates is a significant milestone and reflects our considerable efforts to accelerate the development of our emerging biologicals portfolio. It is our unique plant-based vaccine technology, which acts as a fast, efficient host for the production of antigens for a variety of diseases, that has enabled us to make this progress and respond to the urgent global need for safe and effective treatments and vaccines.

“This is part of our ongoing commitment to innovation and science, which are fundamental to our business. As a company committed to building A Better Tomorrow, we are proud to play our part in the global fight against this virus and – hopefully – we can contribute to the solution.”

With both vaccines reaching these important milestones, the science around tobacco plant-based vaccine development and the unique platform continue to gain momentum.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Source: TechnologyNetworks

Anthraquinones are a class of naturally occurring compounds prized for their medicinal properties, as well as for other applications, including ecologically friendly dyes. Despite wide interest, the mechanism by which plants produce them has remained shrouded in mystery, until now.

New work from an international team of scientists including the Carnegie Institution for Science's Sue Rhee reveals a gene responsible for anthraquinone synthesis in plants. Their findings could help scientists cultivate a plant-based mechanism for harvesting these useful compounds in bulk quantities.

"Senna tora is a legume with anthraquinone-based medicinal properties that have long been recognized in ancient Chinese and Ayurvedic traditions, including antimicrobial and antiparasitic benefits, as well as diabetes and neurodegenerative disease prevention," Rhee explained.

Despite its extensive practical applications, genomic studies of Senna have been limited. So, led by Sang-Ho Kang of the Korean National Institute of Agricultural Sciences and Ramesh Prasad Pandey of Sun Moon University and MIT, the research team used an array of sophisticated genetic and biochemical approaches to identify the first known anthranoid-forming enzyme in plants.

"Now that we've established the first step of the ladder, we can move quickly to elucidate the full suite of genes involved in the synthesis of anthraquinone," said lead author Kang.

Once the process by which plants make these important compounds is fully known, this knowledge can be used to engineer a plant to produce high concentrations of anthraquinones that can be used medicinally.

"The same techniques that we use to help improve the yields of agricultural or biofuel crops can also be applied to developing sustainable production methods for plant-based medicines," Rhee concluded.

Source: Lab Manager

Monash University researchers have created the world’s first bioactive plant-based nanocellulose hydrogel to support organoid growth and help significantly reduce the costs of research into cancer and COVID-19.

This discovery by researchers in BioPRIA (Bioresource Processing Institute of Australia), Monash University’s Department of Chemical Engineering and the Monash Biomedicine Discovery Institute will develop organoids cheaper, faster and more ethically.

The hydrogel can also boost drug screening and disease modelling for infectious diseases, like COVID-19; metabolic diseases, such as diabetes and obesity; and cancer.

The findings, published in Advanced Science, emerge as a promising finding for growth of organoids for essential laboratory testing across the world. With additional testing, this hydrogel could be available to researchers and health professionals across the world in under 12 months.

Nanocellulose gels cost just cents for each 10ml used, compared to $600 or more for the present gold standard.

Most importantly, nanocellulose gels are completely plant-based, preventing the harvesting of animal organs and unknown biomolecules for any advanced medical testing.

Professor Gil Garnier and Dr Rodrigo Curvello from BioPRIA within Monash University’s Department of Chemical Engineering led the analysis.

“These are major obstacles for basic research studies as well as also the translation of organoids to clinics. Alternative matrices able to sustain organoid systems have to reduce costs drastically and to eliminate the unreliability of unfamiliar biomolecules.

“As nanocellulose hydrogel is animal-free, its composition is controlled perfectly and reproducible – unlike the present progress – and fully mimic the human body requirements.”

Organoids are three-dimensional, miniaturised and simplified versions of organs generated in vitro that can replicate behaviors and functionalities of developed organs.

Commonly referred to as’organs in a dish’ or’mini-organs’, organoids are an excellent tool to study fundamental biological processes. During organoids, we can understand how cells interact in an organ, how diseases affect them and the effects of drugs in disease reduction.

Organoids are generated from embryonic, adult, pluripotent or triggered pluripotent stem cells, in addition to from primary healthy or cancerous cells.

For long-term use, organoids are commonly embedded inside an Engelbreth-Holm Swarm (EHS) matrix derived from the reconstituted basement membrane of mouse sarcoma.

Currently, organoid culture is dependent of the expensive and undefined tumour-derived substance that hinders its application in high-throughput screening, regenerative medicine and diagnostics.

“Our study was basically able to utilize an engineered plant-based nanocellulose hydrogel that can replicate the growth of small intestinal organoids derived from mice,” Dr Curvello said.

“It is essentially made from 99.9% water and only 0.1% solids, functionalised with one cell adhesive peptide. Cellulose nanofibers are linked with salts that provide the microenvironment necessary for small intestinal organoid growth and proliferation.

“Engineered nanocellulose gel represents a sustainable alternative for the increase of organoids, contributing to reducing the costs of studies on diseases of international concern, especially in developing nations.”

Source: Microbioz India

For many years, scientists have attempted to use microbial hosts to produce chemicals via a process known as microbial biosynthesis. Recent advances in synthetic biology have bolstered this field of research. In a recent study published in Nature, researchers successfully produced tropane alkaloids – medicines that have a wide variety of applications, including treating conditions as diverse as Parkinson's disease and motion sickness – in yeast. To achieve this, the scientists had to conduct over 30 genetic modifications in parallel. Their feat is the first successful study of its kind at this level of complexity.

Technology Networks spoke with Dr Christina Smolke, lead author of the study, to learn more about microbial biosynthesis platforms and their utility in drug discovery and manufacturing.

Molly Campbell (MC): For our readers that are unfamiliar, please can you discuss the utility of tropane alkaloids in modern medicine?

Christina Smolke (CS): The tropane alkaloids, a class of plant-based anticholinergics, have activities as neuromuscular inhibitors. A number of tropane alkaloids are on the World Health Organization’s List of Essential Medicines and the recently published Food and Drug Administration List of Essential Medicines for their use in treating neuromuscular disorders such as Parkinson’s disease (PD), intestinal disorders and other issues caused by muscle spasms. For example, scopolamine is used to relieve motion sickness and post-operative nausea, and atropine is used to curb the drooling associated with PD or to help maintain cardiac function when intubating COVID-19 patients and placing them on ventilators.

MC: How important are advances in synthetic biology to your field of research?

CS: Advances in synthetic biology have been very important for our work on microbial biosynthesis, especially in terms of advancing the complexity of cell systems that we can engineer. General approaches developed in synthetic biology (such as genome engineering, protein engineering and expression optimization) have been effective for addressing the biosynthesis of relatively simple molecules (i.e., those requiring a handful of enzymes to make), but run into a complexity threshold (which closes off a huge number of potential compounds/products). However, these general approaches alone don’t allow us to reconstruct the full complexity of nature’s chemistries; in order to build complicated medicinal products using a completely bottom up approach, we need not only three or five but sometimes 20 or more enzymes and genes to work together. In plants, these enzymes have often evolved to work together across different cells and tissue types to enable the plant to specialize chemistries for unique reactions and compounds. These natural strategies are typically lost in moving the pathway to a single-celled organism. We established a whole-cell engineering approach to really crack this problem.

MC: How is baker's yeast engineered to produce medicinal alkaloids?

CS: The full reconstruction of tropane alkaloid biosynthesis in baker’s yeast required the functional expression and integration of 26 genes from 10 different organisms (across four kingdoms) and eight gene deletions. The resulting whole-cell system expresses enzymes and transporters across every yeast organelle to truly re-envision the cell as a factory for efficiently assembling the most complex molecules known to humankind.

MC: A huge issue in the synthesis of biopharmaceutical products is scale-up. Can you discuss this issue in relation to using microbial biosynthesis platforms?

CS: Microbial fermentation of biopharmaceuticals has an advantage in scale-up, in that strategies, infrastructure and know-how for fermenting yeast at commercial scale are well established in the space. In addition, biopharmaceutical products are higher value and lower volume than other product classes, such as biofuels or commodity chemicals, and thus the fermentation processes themselves are generally more robust at commercial scale. One of the important variables for the field is downstream processing and being able to develop commercially viable recovery processes for the product from the fermentation broth at scale. In this regard, it is important to tackle the development of the yeast strain, fermentation process and recovery process – in parallel – from the R&D stage, to ensure all facets of the process will work together to reach the desired commercial metrics.

MC: When using microbial biosynthesis platform, how is the safety of the final product assessed?

CS: To date, in using a microbial fermentation process to produce an already approved active ingredient in a medicine, safety is primarily assessed by demonstrating equivalency of the purified product produced via microbial fermentation to the product produced via conventional approaches (e.g., extraction from the plant). Next, there are QA/QC requirements in meeting the USP pharmacopia standards for generic APIs, including impurities and stability requirements.

MC: Are there any challenges associated with mainstream use of microbial-based platforms for drug synthesis?

CS: From a manufacturing process perspective, there are not many challenges that are new to the industry. Specifically, a number of our active ingredients in drugs have been synthesized using microbial fermentation for decades, including many of our antibiotics, statins and even drugs such as recombinant insulin. With recent advances in synthetic biology, we can now use this manufacturing approach to produce more complicated medicinal products, including analgesics, sedatives, neuromuscular blockers and chemotherapeutics.

MC: In your opinion, how will microbial-based platforms for the synthesis of drugs evolve over the next ten years?

CS: Microbial-based biosynthesis platforms set the foundation for a flexible and on-demand replacement for our fragmented and slow-moving drug supply chain. I believe microbial-based biosynthesis will become the main approach for the synthesis of complex natural product-like active ingredients. Rather than the months or years it takes to grow, harvest, and extract molecules from plants, this approach takes days. I also believe there are interesting opportunities when leveraging bioproduction via microbial fermentation to explore more distributed versus centralized production strategies, which will be increasingly important as we see our global supply chains face increasing pressure from pandemics, geopolitical events and environmental disasters.

Source: Technology Networks

A biopharmaceutical company has announced positive Phase 1 trial results of a potential plant-based COVID-19 vaccine.

Researchers at Medicago, based in Quebec City, said they were pleased with the interim results, which demonstrated that 100% of subjects developed “a promising antibody” after receiving two doses of the drug.

"We also observed that the antibody levels were higher after vaccination than those observed in convalescent sera from people who recovered from the disease," said Nathalie Landry, executive vice president of scientific and medical affairs at Medicago.

The company reported that its trial candidates experienced mild and short side effects but didn’t elaborate on the symptoms in an issued press release. Safety followups will continue.

Medicago researchers selected 180 men and women between 18 and 55 years old for the trial. The company hopes to get government approval to enter Phase 2 and then 3 of the trial.

"The positive results of our Phase 1 clinical trial are a step forward in the fight against the COVID-19 pandemic," said Dr. Bruce D. Clark, president and CEO of Medicago.

The news came as coronavirus cases continue to rise in the United States and around the globe. Johns Hopkins University reported that there have been more than 51 million total cases of COVID-19 around the world since the pandemic began. The U.S. surpassed 10 million cases and more than 240,000 deaths in November.

U.S. drugmaker Pfizer, meanwhile, announced Monday that data showed its potential vaccine is 90% effective in preventing the virus. The pharmaceutical company hopes to get the Food and Drug Administration’s Emergency Use Authorization in coming weeks.

Moderna also hopes to receive the same authorization next month, according to Reuters.

A handful of companies, including AstraZeneca, Novavax and Johnson & Johnson are currently in the middle of Phase 3 trials with their COVID-19 vaccine candidates.

Source: FOX 5

A small protein isolated from beetroot is able to block the activity of an enzyme called prolyl oligopeptidase (POP), which breaks down certain hormones and signaling molecules, and is thought to control the body’s inflammatory responses.

According to the researchers, the discovery of this plant-derived protein may make possible new therapies targeting POP, which is increasingly being explored as a target for neurodegenerative and inflammatory disorders like multiple sclerosis (MS) and Alzheimer’s disease.

Many species of plants evolved to develop mechanisms that protect them from pests and herbivores. One such mechanism uses the production of small proteins, or peptides, that are highly resistant to pests and harsh environmental conditions.

Peptide protease inhibitors are a class of peptides that protect plants from bacteria, viruses, and insects by destroying the enzymes these pests use to digest plant tissue. This particular class of peptides is also promising as peptide-based therapy candidates, due to their cysteine bonds that sometimes form “knot-like structures” that make them highly stable in acid environments, as well as highly resilient to degradation.

Of note, cysteine is one of the 23 amino acids that are the building blocks of proteins; when two cysteine residues interact with each other, they are able to make highly stable disulfide bonds that sometimes intertwine to form a knot.

Although many sub-classes of these peptide protease inhibitors have been identified, “there is still a limited understanding of how certain protease inhibitors are distributed within the plant kingdom.”

Researchers at the Center for Physiology and Pharmacology with the Medical University of Vienna and their colleagues described how they discovered a new peptide protease inhibitor from a species of beetroot called Beta vulgaris. This inhibitor shows therapeutic potential based not only on its knot-like structure, but also on its ability to block the activity of the POP enzyme.

While screening B. vulgaris leaves and pulp extracts for peptide protease inhibitors with disulfide bonds, researchers discovered a small peptide they later named Beta vulgaris trypsin inhibitor I, or bevuTI-I for short.

After using mass spectrometry to determine the exact amino acid sequence of bevuTI-I, the team looked for other previously described peptides with similar sequences that could provide clues on the function and properties of the new peptide.

These analyses indicated bevuTI-I’s sequence was similar to trypsin inhibitors found in spinach (S. oleracea) and in the four o’clock plant (Mirabilis jalapa), which belonged to a subfamily of compounds known as knottin trypsin inhibitors. These trypsin inhibitors have a unique “knot-like structure” made up of three disulfide bonds intertwined with each other. (Trypsin is an enzyme that breaks down proteins.)

Additional analyses showed that bevuTI-I could inhibit both trypsin, as expected based on its similarity with other trypsin inhibitors, and POP. Like trypsin, POP is also able to break down proteins and other signaling molecules in the body. This enzyme has also started to be investigated as a potential target for treating certain inflammatory and neurodegenerative disorders due to its ability to control inflammatory responses.

“This means that, in future studies, this group of plant peptides called ‘knottins’, such as those found in beetroot, could potentially provide a drug candidate for treating these diseases,” Christian Gruber, PhD, an associate professor at the center and the study’s senior author, said in a press release.

Researchers also discovered the new bevuTI-I peptide can be found in commercially available beetroot juice, albeit in very small amounts. They added that would be unreasonable to assume the regular consumption of beetroot would protect against inflammatory and neurodegenerative diseases, as at this point it is still unknown if the peptide can be absorbed through the gastrointestinal tract.

“Our study highlights great potential of plant protease inhibitors isolated from beetroot and other related plant species as a valuable source for peptide-based drug discovery for targets involved in diseases such as cancer, neurodegenerative disorders, and immune system related diseases,” the researchers wrote.

The team now plans to further explore the properties certain natural compounds have in developing treatment candidates.

“We are searching through large databases containing genetic information of plants and animals, decoding new types of peptide molecules and studying their structure, aiming to test them pharmacologically on enzymes or cellular receptors … and finally analyzing them in the disease models,” Gruber said.

These researchers successfully used this approach a few years ago to create a treatment candidate for MS, T20K, based on a natural plant peptide called cyclotide. T20K is now licensed to Cyxone, and has shown promising efficacy at lowering the production of pro-inflammatory signaling molecules in MS animal models.

It was also found to be safe and well tolerated in healthy volunteers participating in a Phase 1 trial. A potential Phase 2 trial assessing T20K in MS patients is now being planned.

Source: Multiple Sclerosis

In a recent study, a research group led by Christian Gruber at MedUni Vienna's Institute of Pharmacology isolated a peptide (small protein molecule) from beetroot. The peptide is able to inhibit a particular enzyme that is responsible for the breakdown of messenger molecules in the body. Due to its particularly stable molecular structure and pharmacological properties, the beetroot peptide may be a good candidate for development of a drug to treat certain inflammatory diseases, such as e.g. neurodegenerative and autoimmune diseases.

The peptide that occurs in the roots of beetroot plants belongs to a group of molecules that plants use inter alia as a chemical defence against pests such as e.g. bacteria, viruses or insects. "By analysing thousands of genomic data, our team was able to define a number of new cysteine-rich peptides and assign them phylogenetically in the plant kingdom. In this process, our attention was drawn to a possible function as so-called 'protease inhibitors'. The beetroot peptide can therefore inhibit enzymes that digest proteins," explains Gruber.

The beetroot peptide specifically inhibits prolyl oligopeptidase (POP), which is involved in the breakdown of protein hormones in the body and is therefore able to regulate inflammatory reactions. POP is a much-discussed drug target for neurodegenerative and inflammatory diseases, such as Alzheimer's and multiple sclerosis, for example. "This means that, in future studies, this group of plant peptides called 'knottins', such as those found in beetroot, could potentially provide a drug candidate for treating these diseases."

Peptide can be detected in commercial beetroot juice

The peptide not only occurs in the root vegetables but can also be detected in commercially available beetroot juice -- albeit in very low concentrations. "Although beetroot counts as a very healthy vegetable, it would be unreasonable to hope that dementia could be prevented by regular consumption of beetroot," stresses the MedUni Vienna pharmacologist. "The peptide only occurs in very small quantities and it is not clear whether it can as such be absorbed via the gastrointestinal tract."

Using Nature's blueprint

The research work being conducted by Gruber's laboratory utilized the idea of harnessing Nature's blueprint to develop drug candidates. "We are searching through large databases containing genetic information of plants and animals, decoding new types of peptide molecules and studying their structure, aiming to test them pharmacologically on enzymes or cellular receptors (such as one of the prominent drug target classes, the so-called G protein-coupled receptors) and finally analysing them in the disease models," explains Gruber. Potential drug candidates are chemically synthesised in a slightly modified form based on the natural product, in order to obtain optimised pharmacological properties. This concept appears to be successful: a few years ago the research team generated a drug candidate T20K for MS with a synthesised plant peptide (cyclotide), which has recently been tested successfully in a Phase 1 trial by the Swedish firm Cyxone under a MedUni Vienna licence, and is now being prepared for a Phase 2 clinical trial.

Source: Science Daily

A biopharmaceutical company headquartered in Quebec City, Canada, announced that it has reached an agreement to supply the Government of Canada with up to 76 million doses of its vaccine against COVID-19, subject to Health Canada approval.

The government’s press statement on October 23, 2020, indicated this purchase is enough to vaccinate 38 million people and is the first domestically developed vaccine candidate the Government of Canada has secured, that is targeted against the SARS-CoV-2 coronavirus.

“Access to safe and effective vaccines is critical for Canada, and the government is doing its part to help support innovative Canadian companies in performing the research needed to demonstrate that their products meet Health Canada’s high safety, efficacy, and quality standards," added the Hon. Patty Hajdu, Minister of Health, in the press statement.

Medicago's plant-based platform produced its coronavirus Virus-Like Particle (VLP) vaccine. Medicago's plant-derived vaccine development differs because it uses living plants as bioreactors to produce a non-infectious particle that mimics the target virus, without the use of any live viruses.

Medicago’s proprietary technology Proficia® uses N. benthamiana plants, which is the most widely used experimental host in plant virology, due mainly to the large number of viruses that can successfully infect it. Its weakened immune system, the result of natural genetic changes over millennia, means genetic material can be successfully hosted by the plant and not rejected.

Medicago stated on October 23, 2020, it plans to initiate Phase 2 clinical trials in November, and Phase 3 trials in December 2020.

Source: Precision Vaccination

The results from 2 phase 3 studies demonstrated safety and efficacy of a plant-derived influenza vaccine, thus making both studies the first large-scale trial of any such human vaccine.

Despite the public health threat that the seasonal influenza continues to pose, plant-based manufacturing has the potential to address some of the limitations of current vaccines, such as a potential mismatch between vaccine and circulating strains of influenza.

A team led by Brian Ward, MDCM, Medical Officer at Medicago, conducted the randomized, observer-blind, multinational studies in order to assess the efficacy of a plant-based recombinant quadrivalent virus-like particle (QVLP) influenza vaccine in adults 18-64 years and ≥65 years.

The 18-64 study included 10,160 participants across 73 sites. A smaller per-protocol population (n = 4814) was used to assess the vaccine efficacy while the entire population was included in the safety analysis.

The inclusion criteria were body-mass index <40 kg/m2 as well as good health.

Participants were assigned 1:1 to the QVLP vaccine (30 μg haemagglutinin per strain) or placebo.

The primary outcome sought by the investigators was 70% absolute vaccine efficacy, defined as preventing laboratory-confirmed, respiratory illness caused by antigenically matched influenza strains.

However, only 35.1% (95% CI, 17.9-48.7) absolutely efficacy was achieved for the QVLP population.

In terms of safety profile, 1.1% of those who received the vaccine experienced an adverse an adverse event—versus 1.0% in the placebo group.

Furthermore, 0.1% in both the vaccine and placebo groups had severe treatment-related treatment-emergent adverse events.

In the ≥65 years study, the investigators assessed a total of 12,794 participants across 104 sites, with a per-protocol population of 12,022.

Participants were randomly assigned 1:1 receive the QVLP vaccine (30 μg haemagglutinin per strain) or quadrivalent inactivated vaccine (15 μg haemagglutinin per strain).

The primary outcome for this study was relative vaccine efficacy to prevent laboratory-confirmed influenza-like illness caused by any influenza strain.

Thus, it achieved its primary non-inferiority endpoint with a relative vaccine efficacy of 8.8% (95% CI, -16.7 to 28.7).

The investigators reported that 4.1% of the vaccine-treated participants in the per-protocol subpopulation experienced serious adverse events. As for who received the quadrivalent inactivated vaccine, 4.2% experienced serious adverse events.

And finally, <0.1% of participants in both treatment cohorts had severe treatment-related treatment-emergent adverse events.

“Together, [the results of both trials] show that the plant-derived QVLP vaccine can provide substantial protection against respiratory illness and influenza-like illness caused by influenza viruses in adults,” Ward and team concluded. “QVLP vaccine was well tolerated and no major safety signal arose in participants who received QVLP vaccine across the two studies.”

In a separate commentary, John Tregoning, MA, PhD, Department of Infectious Disease, Imperial College London emphasized the importance and potential of alternative vaccine manufacturing processes.

“The field of plant-derived vaccines has grown a lot in the past 28 years, since it was first shown that viral proteins could be expressed in plants,” he wrote. “There is one licensed plant-derived human therapeutic for Gaucher's disease, but this is the first time a plant vaccine has been tested in a clinical trial. It is a milestone for this technology and sows the seeds for other plant-based vaccines and therapeutics.

He noted the drawback in speed at which plant material can be generated during a pandemic. However, he expressed an optimism that such limitations can be overcome, and thus gestured to Medicago’s phase 1 trial of a plant-derived coronavirus disease 2019 (COVID-19) vaccine.

The study, “Efficacy, immunogenicity, and safety of a plant-derived, quadrivalent, virus-like particle influenza vaccine in adults (18–64 years) and older adults (≥65 years): two multicentre, randomised phase 3 trials,” was published online in The Lancet.

Source: HCP Live

A new research collaboration aims to develop new methods and tools to non-invasively monitor the growth and performance of plants used in the production of Virus-Like Particles (VLPs). In doing so, the research will help to optimize the biotechnology for plant-based vaccine development.

Initiated and supported by the Centre for Entrepreneurial Agri-Technology (CEAT) and ANU Innovation, the project will involve researchers from the National Collaborative Research Infrastructure Strategy (NCRIS) – supported Australian Plant Phenomics Facility (APPF), ANU’s Research School of Biology (RSB) and the ANU College of Engineering and Computer Science (CECS), in collaboration with Canadian biopharmaceutical company, Medicago R&D Inc.

Medicago R&D Inc uses a proprietary plant-based technology to develop vaccines and protein-based therapeutics. Key to their technology is the production of Virus-Like Particles (VLPs) as vaccines. VLPs mimic the structure of viruses and can induce an immune response without causing an infection. When purified, VLPs have the potential to be used as vaccines against a range of viruses, such as influenza, rotavirus, and norovirus.

Medicago’s proprietary technology is rapid, versatile, and scalable. Importantly, its recombinant technology allows the production of a vaccine that can match the circulating strains, such as in the case of seasonal influenza.

A five-year collaboration agreement between ANU and Medicago has recently been signed, with the collaboration consisting of multiple projects, starting with a $1M project to take place over 14 months.

In this initial project, the APPF’s Plant Phenomics Group at ANU – that includes Tim Brown and Richard Poire-Lassus – is contributing its full range of facilities and expertise in phenomics, bioinformatics, and data visualisation, as well as access to state of the art equipment and infrastructure such as hyperspectral scanning, and sophisticated controlled environment growth chambers.

As Tim Brown, APPF’s ANU Node director, says, “This technology is very exciting, delivering the capacity to use plants to rapidly make vaccines. To be able to contribute ANU/APPF’s advanced phenotyping know-how and technologies to the project is really special.”

During the initial project, CECS will be contributing the expertise of Professor Hongdong Li and Liang Zheng.

Hongdong Li from CECS says he is “pleased to be supplying expertise in the application of computer-based approaches to develop deep-learning models of plant growth.”

Together with Medicago R&D Inc, the ANU partners will work to develop new methods and tools to non-invasively monitor the growth and performance of plants used in the production of VLPs.

Owen Atkin, director, Centre for Entrepreneurial Agri-Technology (CEAT) is proud that CEAT has been able to play a central role in bringing together the APPF, RSB, CECS and Medicago R&D Inc.

“The collaboration highlights the value of university-based, interdisciplinary teams working with an industry partner to help address complex challenges of global significance – in this case, the urgent need to improve global access to vaccines,” says Atkin.

Source: Seed World

The secret of how fibre shapes the structure of plant cell walls has been revealed, with potentially wide-ranging applications ranging from nutrition and health to agriculture.

Researchers from The University of Queensland and KTH Royal Institute of Technology in Sweden have uncovered the mechanics of how plant cell walls balance the strength and rigidity provided by cellulose with its ability to stretch and compress.

UQ Director of the Centre for Nutrition and Food Sciences Professor Mike Gidley said the team identified that a family of cell wall polymers -- hemicelluloses -- played a critical role in balancing the need for rigidity with the flexibility to bend without breaking.

"This discovery is important for understanding dietary fibre properties in nutrition, but also for applications in medicine, agriculture and a range of other industries," Professor Gidley said.

"Plants don't have a skeleton, and their structures can range from soft, floppy grasses to the majestic architecture of a Eucalypt tree, with the key differences lying in their cell wall fibre structures."

The diversity of plant structures results from the three core building blocks of plant fibre -- cellulose, hemicellulose and lignins -- in the plant cell walls.

"Lignins provide the water-proofing in woody fibre and cellulose is the rigid scaffolding material in almost all plant types, but the mechanical function of hemicellulose was something of a mystery," Professor Gidley said.

Professor Gidley and Dr Deirdre Mikkelsen, in collaboration with Dr Francisco Vilaplana at KTH's Wallenberg Wood Science Centre, experimented with two major components of hemicellulose -- with dramatic effect.

"We tested the properties of cellulose when adding different proportions of the two components, and found that 'mannans' improved compression while 'xylans' drastically increase its stretchiness," Dr Mikkelsen said.

"We generated modified cellulose material in the laboratory that could be stretched to twice its resting length -- the equivalent to watching a wet sheet of paper being stretched to double its length without tearing."

The team said its discovery had many applications, including in wound care and in the texture of plant foods.

"This information is also of interest for gut microbiome research in understanding more about how plant cells walls, or fibre, break down in the gut," Professor Gidley said.

"Complex plant fibre is already processed for low value applications, but high value materials are usually made from pure (bacterial) cellulose.

"Our work creates the basis for a new cellulose chemistry in which xylans and mannans are added to make composites with useful properties.

"This means new possibilities for developing better, environmentally-sustainable plant-based materials, as well as selecting natural plant fibres with desirable properties in agriculture and food."

Source: Science Daily

Each year fungal diseases affect billions of people globally, causing an estimated 1.6 million deaths. Infections resistant to treatment are a growing problem, particularly in patients with weakened immune systems, such as those with HIV. Since few effective antifungal drugs exist, it is imperative to understand the nature of fungal resistance and how it develops. Thankfully, investigators at the University of Edinburgh have just made a discovery that could be the key to how resistance mechanisms grow over time.

Amazingly, the research team discovered that fungi could develop drug resistance without changes to their DNA. The findings from the new research—published recently in Nature through an article entitled “Epigenetic gene silencing by heterochromatin primes fungal resistance“—finds that resistance can emerge in fungi without genetic changes. Instead, the fungi exhibit epigenetic changes suggesting that many causes and cases of antifungal resistance could have been previously missed.

The team of scientists from the University of Edinburgh’s Wellcome Centre for Cell Biology studied the emergence of resistance in yeast, Schizosaccharomyces pombe, by treating it with caffeine to mimic the activity of antifungal drugs.

“Our team is excited about the possible implications that these findings may have for understanding how plant, animal, and human fungal pathogens develop resistance to the very limited number of available and effective antifungal drug treatments,” noted senior study investigator Robin Allshire, PhD, a professor at the Wellcome Centre for Cell Biology.

The researchers discovered that the resulting resistant yeast had alterations in special chemical tags that affect how their DNA is organized. Some genes became packed into structures known as heterochromatin, which silences or inactivates underlying genes, causing resistance as a result of this epigenetic change.

“We show that heterochromatin-dependent epimutants resistant to caffeine arise in fission yeast grown with threshold levels of caffeine,” the authors wrote. “Isolates with unstable resistance have distinct heterochromatin islands with reduced expression of embedded genes, including some whose mutation confers caffeine resistance. Forced heterochromatin formation at implicated loci confirms that resistance results from heterochromatin-mediated silencing. Our analyses reveal that epigenetic processes promote phenotypic plasticity, letting wild-type cells adapt to unfavorable environments without genetic alteration. In some isolates, subsequent or coincident gene-amplification events augment resistance.”

The authors went on to state that caffeine affects two anti-silencing factors: Epe1 is downregulated, reducing its chromatin association, and a shortened isoform of Mst2 histone acetyltransferase is expressed. Thus, heterochromatin-dependent epimutation provides a bet-hedging strategy allowing cells to adapt transiently to insults while remaining genetically wild type. Isolates with unstable caffeine resistance show cross-resistance to antifungal agents, suggesting that related heterochromatin-dependent processes may contribute to resistance of plant and human fungal pathogens to such agents.”

This discovery could pave the way for new therapies to treat resistant infections by modifying existing epigenetic drugs or developing new drugs that interfere with fungal heterochromatin.

Improved fungicides to treat food crops could limit agricultural losses and also reduce the number of resistant fungal strains in the environment that continue to fuel increased infections in humans.

Source: GEN

Researchers report the first successful microbial biosynthesis of the tropane alkaloids hyoscyamine and scopolamine, a class of neuromuscular blockers naturally found in plants in the nightshade family.

Describing a first-in-class fermentation-based approach for producing complex molecules, the paper lays the foundation for a controlled, flexible, cell-based manufacturing platform for essential medicines that currently rely on crop farming, according to research leader Christina Smolke, PhD, professor of bioengineering at Stanford University and CEO and co-founder of Antheia, a synthetic biology company making next-generation plant-inspired medicines.

The tropane alkaloids hyoscyamine and scopolamine are used in treating neuromuscular disorders such as Parkinson’s, intestinal disorders, and other issues caused by muscle spasms. Currently, the global supply of these medicinal tropane alkaloids relies on intensive cultivation of nightshade plants, as direct chemical synthesis of these medical agents is not commercially viable.

As a result, this class of drugs is subject to global supply risks. The current agricultural-based supply chain coupled with increasing demand has resulted in recurring shortages of tropane alkaloid-based medicines, such as atropine, an antimuscarinic agent used to reduce salivation before surgery, and transdermal scopolamine patches used to prevent nausea and vomiting.

“Tropane alkaloids from nightshade plants are neurotransmitter inhibitors that are used for treating neuromuscular disorders and are classified as essential medicines by the World Health Organization. Challenges in global supplies have resulted in frequent shortages of these drugs,” the investigators wrote.

“Further vulnerabilities in supply chains have been revealed by events such as the Australian wildfires and the COVID-19 pandemic. Rapidly deployable production strategies that are robust to environmental and socioeconomic upheaval are needed.

“Here we engineered baker’s yeast to produce the medicinal alkaloids hyoscyamine and scopolamine, starting from simple sugars and amino acids. We combined functional genomics to identify a missing pathway enzyme, protein engineering to enable the functional expression of an acyltransferase via trafficking to the vacuole, heterologous transporters to facilitate intracellular routing, and strain optimization to improve titers.

“Our integrated system positions more than twenty proteins adapted from yeast, bacteria, plants, and animals across six sub-cellular locations to recapitulate the spatial organization of tropane alkaloid biosynthesis in plants. Microbial biosynthesis platforms can facilitate the discovery of tropane alkaloid derivatives as new therapeutic agents for neurological disease and, once scaled, enable robust and agile supply of these essential medicines.”

“This paper is an exciting breakthrough for the pharmaceutical industry and a positive signal for the next phase of growth in synthetic biology,” said Smolke. “Publishing our efforts to produce complex molecules like tropane alkaloids is a critical proof point for realizing an advanced manufacturing model that offers greater efficiency, consistency, and quality in global medicine production.

“Beyond the potential impact on pharma, the ability to functionally express, integrate, and orchestrate genetic and biochemical functions across kingdoms and species will help realize synthetic biology’s promise across several industries and applications.”

Since the inception of synthetic biology, efforts have abounded to use microbial hosts like yeast to produce a diversity of chemicals, with most successful demonstrations applied to compounds that require the introduction of limited numbers of non-native genes. To date, microbial biosynthesis has been demonstrated for a limited number of relatively simple medicinal compounds, including antimalarials and cannabinoids.

One of the key challenges in reconstructing more complex plant-based biosyntheses in microbes is that plants have evolved extensive strategies for spatially distributing enzymes (and associated chemistries) across cellular compartments, cell types, and even tissues, strategies that cannot be readily recapitulated in single-cell yeast.

The full reconstruction of tropane alkaloid biosynthesis in yeast presented in this paper is the most advanced example of a microbial cell factory to date, requiring the functional expression and integration of 26 genes from 10 different organisms (across 4 kingdoms) and 8 gene deletions. The resulting whole-cell system expresses enzymes and transporters across every yeast organelle to truly re-envision the cell as a factory for efficiently assembling the most complex molecules known to humankind.

The tropane alkaloids are the latest category of highly complex plant-based medicinal compounds Smolke’s lab has produced via yeast fermentation. Smolke’s earlier pioneering work demonstrated the biosynthesis of another class of plant-based medicines (benzylisoquinoline alkaloids), and this paper further highlights the flexibility and power of brewer’s yeast as a platform for synthesizing the most valuable and complex molecules.

This whole-cell bioengineering approach to biosynthesis underlies Smolke’s work both in her Stanford lab and at Antheia, which brings together functional genomics, protein engineering, and strain optimization to enable on-demand and at-scale production of plant-inspired medicines, and to dramatically expand the possibilities for discovering new medicines.

“This study is setting new standards for how yeast can be recruited for production of complex plant natural products,” said Jens Nielsen, PhD, professor of systems biology, Chalmers University of Technology, Sweden. “Assembly of a pathway consisting of more than 30 plant enzymes in yeast is truly impressive, and the learnings from this study will enable a far wider application of yeast-based production of complex plant natural products that can be used as pharmaceuticals and nutraceuticals.”

Source: GEN

Plants have a unique ability to safeguard themselves against pathogens by closing their pores—but until now, no one knew quite how they did it. Scientists have known that a flood of calcium into the cells surrounding the pores triggers them to close, but how the calcium entered the cells was unclear.

A new study by an international team including University of Maryland scientists reveals that a protein called OSCA1.3 forms a channel that leaks calcium into the cells surrounding a plant's pores, and they determined that a known immune system protein triggers the process.

The findings are a major step toward understanding the defense mechanisms plants use to resist infection, which could eventually lead to healthier, more resistant and more productive crops. The research paper was published on August 26, 2020 in the journal Nature.

"This is a major advance, because a substantial part of the world's food generated by agriculture is lost to pathogens, and we now know the molecular mechanism behind one of the first and most relevant signals for plant immune response to pathogens—the calcium burst after infection," said José Feijó, a professor of cell biology and molecular genetics at UMD and co-author of the study. "Finding the mechanism associated with this calcium channel allows further research into its regulation, which will improve our understanding of the way in which the channel activity modulates and, eventually, boosts the immune reaction of plants to pathogens."

Plant pores—called stomata—are encircled by two guard cells, which respond to calcium signals that tell the cells to expand or contract and trigger innate immune signals, initiating the plant's defense response. Because calcium cannot pass directly through the guard cell membranes, scientists knew a calcium channel had to be at work. But they didn't know which protein acted as the calcium channel.

To find this protein, the study's lead author, Cyril Zipfel, a professor of molecular and cellular plant physiology at the University of Zurich and Senior Group Leader at The Sainsbury Laboratory in Norwich, searched for proteins that would be modified by another protein named BIK1, which genetic studies and bioassays identified as a necessary component of the immune calcium response in plants.

When exposed to BIK1, one protein called OSCA1.3 transformed in a very specific way that suggested it could be a calcium channel for plants. OSCA1.3 is a member of a widespread family of proteins known to exist as ion channels in many organisms, including humans, and it seems to be specifically activated upon detection of pathogens.

To determine if OSCA1.3 was, in fact, the calcium channel he was looking for, Zipfel's team reached out to Feijó, who is also an affiliate professor in the College of Agriculture and Natural Resources at UMD and is well known for identifying and characterizing novel ion channels and signaling mechanisms in plants. Erwan Michard, a visiting assistant research scientist in Feijó's lab and co-author of the paper, conducted experiments that revealed Zipfel's BIK1 bait triggers OSCA1.3 to open up a calcium channel into a cell and also explained the mechanism for how it happens.

BIK1 only activates when plants get infected with a pathogen, which suggests that OSCA1.3 opens a calcium channel to close stomata as a defensive, immune system response to pathogens.

"This is a perfect example of how a collaborative effort between labs with different expertise can bring about important conclusions that would be difficult on solo efforts," Feijó said. "This fundamental knowledge is badly needed to inform ecology and agriculture on how the biome will react to the climatic changes that our planet is going through."

Feijó will now incorporate this new knowledge of the OSCA1.3 calcium channel into other areas of research in his lab, which is working to understand how the mineral calcium was co-opted through evolution by all living organisms to serve as a signaling device for information about stressors from infection to climate change.

"Despite the physiological and ecological relevance of stomatal closure, the identity of some of the key components mediating this closure were still unknown," Zipfel said. "The identification of OSCA1.3 now fills one of these important gaps. In the context of plant immunity this work is particularly apt in 2020, the UN International Year of Plant Health.

Reference

Thor, K., Jiang, S., Michard, E. et al. The calcium-permeable channel OSCA1.3 regulates plant stomatal immunity. Nature (2020). https://doi.org/10.1038/s41586-020-2702-1

Source: Technologynetworks

Both the American Botanical Council and the American Herbal Products Association strongly discourage sales or marketing of dietary supplements that contain any part of the oleander plant.

Oleandrin, a cardiac glycoside found in the oleander plant – a highly toxic plant – has been drawing attention the last few days due its potential use for treatment of COVID-19. Both the American Botanical Council (ABC; Austin, TX) and the American Herbal Products Association (AHPA; Silver Spring, MD) are strongly discouraging the sale or marketing of dietary supplements that contain any part of the oleander plant (Nerium oleander) or its constituent, oleandrin, and warned the public about the substantial toxicity associated with all parts of the plant.

ABC warns consumers not to ingest any parts of the plant, or capsules, tablets, teas, or extract preparations made from leaves or other parts of the oleander plant because it contains chemicals that can cause serious effects to the human heart, including death.

AHPA also urges physical and online retailers to refrain from offering any such products for sale, and AHPA cautions consumers to avoid oral consumption of oleander or oleandrin.

The warning came as a result of recent media reports that President Trump may be considering asking (or may have asked) the FDA to approve the drug product called oleandrin as a potential treatment for COVID-19. Oleandrin, as a purified pharmaceutical investigative drug product, has been researched for its potential applications in cancer treatment and as an antiviral agent by pharmaceutical drug-development company Phoenix Biotechnologies. Some of the studies in these areas have shown successful results in laboratory research, but it has not been tested in humans with COVID-19.

Media coverage on oleandrin has been seen on CNN, and in articles on the Newsweek and Men’s Health websites, among other sources. In the CNN coverage, CNN’s Chief Medical Correspondent Dr. Sanjay Gupta emphasized the extreme toxicity of the oleander plant itself and cautioned consumers against using it.

“To be clear, ABC applauds appropriate scientific research into medicinal plants and fungi as sources of new medicines,” ABC founder and executive director Mark Blumenthal said in a press release. “We also acknowledge the very promising medical research conducted by Phoenix Biotechnologies and their oleandrin formulations. However, ABC emphasizes the distinction between a scientifically studied, chemically defined experimental new drug compound from a widely known poisonous plant and a simple home-made pill, tea, or extract made from the plant’s various parts. With respect to oleander, all parts of the plant are highly toxic, dangerous, and life-threatening when ingested. Consumers should not, ever, try to make a home-made remedy from or self-treat with oleander.”

Source: Nutritional Outlook

While use of cannabis remains illegal in many parts of the world, it has been beneficial in curing many underlying diseases

The quest to develop a Covid-19 vaccine is seeing pharmaceutical companies test and try plant-based products, including cannabis and tobacco leaves. This includes companies such as Kentucky Bioprocessing, Novavax, and ZYUS Life Sciences, Moneycontrol reported.

Tobacco-based vaccine

US-based Kentucky Bioprocessing is developing a vaccine against SARS-CoV-2, which is based on tobacco.

The World Health Organisation (WHO) revealed in its draft that the Covid-19 vaccine being developed by Kentucky is under Phase 1/2 trials. The firm is testing its experimental vaccine on 180 healthy volunteers in the US.

Kentucky Bioprocessing is harvesting tobacco plants that have been injected by the potential antigen which was developed by cloning a portion of SARS-CoV-2’s genetic sequence.

Following harvesting of the plant, the antigen is purified and administered as a vaccine.

Cannabis-based vaccine

While use of cannabis remains illegal in many parts of the world, it has proven beneficial in curing many underlying diseases.

ZYUS Life Sciences announced in July that it has reached a positive milestone in the development of Covid-19 vaccine components by achieving plant-based expression, isolation, and purification of a potential antigen for a SARS-CoV-2 vaccine — providing proof of concept for plant-based Covid-19 antigen production.

Cannabinoids are derived from the cannabis plant, including ∆9-tetrahydrocannabinol (THC), cannabidiol (CBD), or a combination of THC and CBD. Synthetic cannabinoids for medicinal use typically mimic the effects of specific cannabinoids such as THC.

In an interview with Canadian TV channel Global News, Zyus CEO Brent Zettl said: “The cannabis side of it really just helped us sort of determine the best ways to manufacture drugs, going forward.”

ZYUS noted that it has tested and demonstrated that the plant-based SARS-CoV-2 protein is recognised by antibodies in the serum of recovered Covid-19 patients, suggesting that plant-based protein, in this form of a vaccine, could potentially provide protection from Covid-19 infection.

Source: Businessline

Chemists at Scripps Research have efficiently created three families of complex, oxygen-containing molecules that are normally obtainable only from plants.

These molecules, called terpenes, are potential starting points for new drugs and other high-value products -- marking an important development for multiple industries. In addition, the new approach could allow chemists to build many other classes of compounds.

The key to this new method of making molecules is the harnessing, or hijacking, of natural enzymes -- from bacteria, in this case -- to assist in complex chemical transformations that have been impractical or impossible with synthetic chemistry techniques alone, says principal investigator Hans Renata, PhD, an assistant professor in the Department of Chemistry at Scripps Research.

Natural enzymes that help build molecules in cells usually perform only one or two highly specific tasks. But the Scripps Research team showed that natural enzymes, even without modification, can be made to perform a wider range of tasks.

"We think that in general, enzymes are a mostly untapped resource for solving problems in chemical synthesis," Renata says. "Enzymes tend to have some degree of promiscuous activity, in terms of their ability to spur chemical reactions beyond their primary task, and we were able to take advantage of that here.

Tapping into enzymes' hidden talents

Enzymes help build molecules in all plant, animal and microbial species. Inspired by their efficiency in constructing highly complex molecules, chemists for more than half a century have used enzymes in the lab to help build valuable compounds, including drug compounds -- but usually these compounds are the same molecules the enzymes help build in nature.

Harnessing natural enzymes in a broader way, according to their basic biochemical activity, is a new strategy with vast potential.

"Our view now is that whenever we want to synthesize a complex molecule, the solution probably already exists among nature's enzymes -- we just have to know how to find the enzymes that will work," says senior author Ben Shen, PhD, chair of the Department of Chemistry on the Florida campus and director of Scripps Research's Natural Products Discovery Center.

The team succeeded in making nine terpenes known to be produced in Isodon, a family of flowering plants related to mint. The complex compounds belong to three terpene families with related chemical structures: ent-kauranes, ent-atisanes, and ent-trachylobanes. Members of these terpene families have a wide range of biological activities including the suppression of inflammation and tumor growth.

A recipe for synthesis success

The synthesis of each compound, in less than 10 steps for each, was a hybrid process combining current organic synthesis methods with enzyme-mediated synthesis starting from an inexpensive compound called stevioside, the main component of the artificial sweetener Stevia.

The chief hurdle was the direct replacement of hydrogen atoms with oxygen atoms in a complex pattern on the carbon-atom skeleton of the starting compound. Current organic synthesis methods have a limited arsenal for such transformations. However, nature has produced many enzymes that can enable these transformations -- each capable of performing its function with a degree of control unmatched by man-made methods.

"Being an interdisciplinary research group, we were fully aware of the limitations of current organic synthesis methods, but also of the many unique ways that enzymes can overcome these limitations -- and we had the insights to combine traditional synthetic chemistry with enzymatic methods in a synergistic fashion," Renata says.

The three enzymes used, which were identified and characterized by Shen, Renata and colleagues only last year, are produced naturally by a bacterium -- one of the 200,000-plus species in the Microbial Strain Collection at Scripps Research's Natural Products Discovery Center.

"We were able to use these enzymes not only to modify the starting molecules, or scaffolds as we call them, but also to turn one scaffold into another so that we could transform a terpene from one family into a terpene from a different family," says second author Emma King-Smith, a PhD student in the Renata lab.

The chemists now intend to use their new approach to make useful quantities of the nine compounds, as well as chemical variants of the compounds, and, with collaborating laboratories, explore their properties as potential drugs or other products.

"With our strategy, we can make these highly oxidized diterpenes much more easily and in larger quantities than would be possible by isolating them from the plants where they are found naturally," says first author Xiao Zhang, PhD, a postdoctoral research associate in the Renata lab.

Just as importantly, the researchers say, they are working to identify reactions and enzymes that will allow them to extend their approach to other classes of molecules.

Central to all these efforts is the ongoing development of methods to sift through the DNA of microbes and other organisms to identify the enzymes they encode -- and predict the activities of those enzymes. Billions of distinct enzymes exist in plants, animals, and bacteria on Earth and only a tiny fraction of them have been catalogued to date.

"We're excited about the potential of discovering new and useful enzymes from our strain library here at Scripps Research," Renata says. "We think that will enable us to solve many other problems in chemical synthesis."

Source: Science Daily

Hanmi Science CEO Lim Chong Yoon (left) and Theragen Bio Huang Tae Soon took a photo after signing an MOU for joint development and research on genome-based infectious disease diagnosis at the headquarters of Hanmi Pharm in Seoul.

Hanmi Science announced on the 30th that it had signed an MOU with Theragen Bio for joint development and research cooperation with genome-based infectious disease diagnosis at the headquarters of Hanmi Pharm.

Terazen, a leading biological company in South Korea based on genetic analysis technology, studies the use of big data and new antigens(NeoAntigen) for new drug development and accurate diagnosis.

Hanmi Science and Theragen Bio are planning to expand the scope of application to the research field of precision diagnostic analysis for epidemic treatment in an innovative way by analyzing a variety of specific genetic factors of novel coronavirus pneumonia patients.

This genome analysis method will be used for next-generation precision analysis of the unreleased corona treatment "Hanmi COVID MDT Program". By finding out the source of infection, it can be used to accurately define the patient group and cure diagnosis method, thus being used in COVID-19 drug development. In addition, after the Food and Drug Safety Department evaluates the clinical effectiveness, it will be preserved as a big data for pandemic as a kind of health care tool for national disease management.

Hanmi Science defined the promising bio-venture bio-app and plant-based COVID-19 green vaccine project as a green bio new deal on June 16. In addition to the "Cydio Cigma" six visions (online education, digital biology, oral biology, urban biology, green biology and marine biology), the new generation of diagnosis based on big data and artificial intelligence will be another pipeline to be promoted as the commercialization plan of the new digital biology policy.

"After the diagnostic kit that led to the success of K quarantine, the precise diagnostic business, the future cash cow, will become another biomedical science industry for K-Bio, along with the development of new drugs," said Lim Chong Yoon, CEO of Hanmi Science.

Source: Financial News

韩美科技代表林钟润（左）和Terazen生物公司代表黄泰淳最近在首尔慰礼城大路韩美药品总公司签署了联合开发研究基于遗传因子的传染病诊断的谅解备忘录后，二者合影留念。

韩美科技30日表示，在位于首尔慰礼城大路的韩美药品总公司与Terazen生物公司签署了联合开发研究基于基因组的传染病诊断的谅解备忘录。

Terazen生物公司是韩国领先的生物公司，以遗传因子分析技术为基础，研究利用大数据和新抗原进行新药开发和精确诊断。

韩美科技和Terazen生物公司计划通过分析新型冠状病毒肺炎患者的多种特定遗传因子，以其创新方式将适用范围扩大至整个流行病治疗的精密诊断分析法的研究领域。

该遗传因子分析法将用于目前尚未公开的新型冠状病毒药物“韩美COVID MDT计划”的新一代精密分析。通过查明感染病源等方式，可以将其用于准确定义患者群体和治愈诊断法等，从而用于新型冠状病毒的药物开发。此外，在食品药品安全部对临床有效性进行评估后，将作为大数据保存下来，作为国家疾病管理的一种保健医疗方案。

韩美科技于6月16日将颇有前景的生物风险生物应用程序和基于植物的新型冠状病毒肺炎绿色疫苗项目定义为绿色生物新政项目。并且作为"Cydio Cigma"6大愿景（网络教育、数字生物、口服生物、城市生物、绿色生物、海洋生物）的另一种方式，将以大数据、人工智能为基础的新一代诊断事业作为数字生物新政商业化计划来推进。

韩美科技代表林钟润表示：“继诊断试剂盒帮助K检疫取得成功后，新一代备受瞩目的精密诊断业务将与新药开发将成为K生物的又一个医疗科学新政产业。”

来源：金融新闻

한미사이언스 임종윤 대표(왼쪽)와 테라젠바이오 황태순 대표가 최근 서울 위례성대로 한미약품 본사에서 유전체 기반 감염병 진단법 공동 개발 연구협력 MOU를 체결한 후 기념촬영을 하고 있다.

한미사이언스는 테라젠바이오와 서울 위례성대로 한미약품 본사에서 유전체 기반 감염병 진단법 공동 개발 연구협력 MOU를 체결했다고 30일 밝혔다.

테라젠바이오는 유전체 분석 기술력을 바탕으로 빅데이터 및 신생항원(NeoAntigen) 등을 활용한 신약개발과 정밀진단을 연구하는 국내 대표 바이오 기업이다.

한미사이언스와 테라젠바이오는 코로나19 환자의 여러 특정 유전체 분석을 통해 혁신적인 방법으로 유행병 치료 전반에 사용될 정밀 진단 분석법 연구로 확장해 나갈 계획이다.

이 유전체 분석법은 현재까지 미공개된 코로나 치료제 '한미 COVID MDT 프로그램'의 차세대 정밀 분석에 활용될 예정이다. 이는 감염병 원인 규명 등을 통해 정확한 환자군 정의와 완치 진단법 등 코로나 치료용 신약 개발과정에서 사용될 수 있다. 또 식약처의 임상 유효성 평가 후에는 국가적 질병 관리를 위한 일종의 보건의료 툴로서, 판데믹에 대비한 빅데이터로 보전될 예정이다.

한미사이언스는 지난 6월 16일 유망 바이오벤처 바이오앱과도 식물 기반 코로나19 그린 백신 프로젝트를 그린 바이오 뉴딜 사업으로 정의한 바 있다. '싸이디오 시그마' 6대 비전(사이버 교육, 디지털 바이오, 오럴 바이오, 시티 바이오, 그린 바이오, 마린 바이오)의 또 다른 파이프라인으로서 빅데이터, 인공지능 기반 차세대 진단 사업을 디지털 바이오의 뉴딜 상업화 계획으로 추진해 나갈 방침이다.

한미사이언스 임종윤 대표는 "K방역의 성공을 이끈 진단키트 이후, 차세대 먹거리인 정밀 진단 사업은 신약개발과 더불어 K바이오의 또 하나의 의료 과학 뉴딜 산업이 될 것"이라고 말했다.

출처 : 파이낸셜 뉴스

A study published in the June 2020 edition of the peer-reviewed journal Horticulturae shows that cycads, which are in decline and among the world's most threatened group of plants, provide an important service to their neighboring organisms. The study, completed by researchers from the Western Pacific Tropical Research Center at the University of Guam and the Montgomery Botanical Center in Miami, found that at least two cycad species share nitrogen and carbon through the soil, thereby creating habitable environments for other organisms.

"The new knowledge from this study shows how loss of cycad plants from natural habitats may create detrimental ripple effects that negatively influence the other organisms that evolved to depend on their ecosystem services," said Patrick Griffith, executive director of the Montgomery Botanical Center.

Cycad plants host nitrogen-fixing cyanobacteria within specialized roots. The tiny microbes willingly share the newly acquired nitrogen with their hosts as their contribution to a symbiosis that benefits both organisms.

Research teams at the University of Guam have long been studying the nutrient relations of Cycas micronesica throughout its endemic range, according to Adrian Ares, associate director of the Western Pacific Tropical Research Center.

"This unique arborescent cycad species is of cultural and ecological importance, and the findings illuminate new knowledge about the ecosystem services that are provided by the plant," Ares said.

The study focused on the concentrations in soil of three elements that impact the growth and development of living organisms. In soils nearby the cycad plants, nitrogen and carbon increased to concentrations that exceeded those of soils that were distant from the plants. In contrast, phosphorus concentrations were depleted in the soils nearby the cycad plants when compared to the distant soils.

"In addition to the direct contributions of carbon and nitrogen to the bulk soils, the chemical changes imposed by the cycad plants created niche habitats that increased spatial heterogeneity in the native forests," Ares said, adding that ecosystems with high biodiversity are generally more resistant to damage by threats and more resilient after the negative impacts.

The niche spaces created by the cycad plants provide the soil food web with a microhabitat that differs from the surrounding forest soils. These soils imprinted by the cycad plants benefit the organisms that exploit spaces characterized by greater nitrogen levels relative to phosphorus and greater carbon levels relative to phosphorus. Scientists call these elemental relationships "stoichiometry," and much has been studied about the importance of these relationships to organismal health and productivity.

The model cycad plants that were employed for the study included two of the cycad species that are native to the United States.

"This study was apropos because the Montgomery Botanical Center is positioned within Zamia integrifolia habitat in Miami, Fla., and the Western Pacific Tropical Research Center is within Cycas micronesica habitat in Mangilao, Guam," Griffith said.

The Florida species is the only cycad species that is native to the continental United States, and the Guam species is the only Cycas species native to the United States.

"Both research teams were gratified to successfully answer questions that were asked of the botanical denizens that have long resided in the respective local forests," Griffith said.

Source: EurekAlert!

Fungal diseases cause substantial losses of agricultural harvests each year. The fungus Botrytis cinerea causing gray mold disease is a major problem for farmers growing strawberries, grapes, raspberries, tomatoes and lettuce. To mitigate the problem, they often resort to applying chemical fungicides which can lose their effectiveness over time. Danforth Center scientists, Dilip Shah, Ph.D., research associate member, Siva Velivelli, Ph.D., postdoctoral associate, Kirk Czymmek, Ph.D., principal investigator and director, Advanced Bioimaging Laboratory and their collaborators at the Pacific Northwest National Laboratory have identified a sub class of peptides in the nodules of the legume, Medicago truncatula that proved effective in inhibiting growth of the fungus causing gray mold. The results of their research, Antifungal symbiotic peptide NCR044 exhibits unique structure and multifaceted mechanisms of action that confer plant protection, were recently published in the journal, Proceedings of the National Academy of Sciences

"We are excited about the possibility of developing this class of peptides as a spray-on fungicide that would provide farmers with an environmentally friendly alternative to chemical fungicides for pre- and post-harvest management of fungal diseases," said Dilip Shah. "When applied to crops, the peptides will eventually break down to amino acids in the soil and be used by beneficial microbes as an energy source."

Medicago truncatula is a relative of alfalfa. Shah and his team produced recombinantly large quantities of the highly charged NCR044 peptide that is expressed in the nodules of this legume. They then applied the peptide in low concentrations to tobacco and tomato plants in the lab and challenged the plants with the gray mold fungus. The plants showed significant protection from this fungal disease.

To understand the antimicrobial mechanism within the cell, they collaborated with Czymmek, who is also a mycologist and has studied fungal cell biology for many years. Using time-lapse confocal and super resolution microscopy, the team was able to observe dynamically how the peptide binds to fungal spores and germlings, how it is internalized and where it goes inside the fungal cell. One key finding here was the confirmation that the peptide concentrated in the nucleolus, the organelle where ribosomal assembly takes place.

"It was a pleasure to work with Dilip and his team. As a young scientist, Siva, was able to move diligently across a very diverse set of platforms and techniques, following-up on leads from the scientific data. Ultimately, he was able to apply these corroborating techniques and uncover significant new information to create robust conclusions about the research project," said Czymmek, "It was really great science."

The unique team of scientists with expertise in fungal and plant cell biology combined with advanced imaging capabilities allowed them to make critical interpretations and confirm their hypotheses. Their collaborator and co-author on the paper, Garry Buchko, Ph.D. at the Pacific Northwest National Laboratory solved the first three-dimensional structure of a nodule-specific peptide revealing a largely disordered, and highly dynamic, peptide structure containing a short anti-parallel β-sheet, tiny α-helix, and when oxidized, two stabilizing disulfide bonds.

Source: PHYS

Hanmi Science (CEO Lim Chong-yoon, Hanmi Group Holding Company) and a promising bioventure Bioapp (CEO Son Eun-joo), which is developing various plant-based antigen proteins, potential vaccine candidates against COVID-19, entered into an R&D cooperation agreement on June 16, and announced the results of high antibody response of their candidates verified in animal experiments with mice and guinea pigs on July 9th.

Along with this, Professor Kim Dong-min of Chosun University, School of Medicine and his team evaluated efficacies for Bioapp’s antigens with various adjuvants from Curatis. The research team confirmed that cell-mediated and humoral immune responses were activated after 2 doses, showing 16,000 binding antibody titer in the ELISA. Bioapp said, “We are planning to assess the capability of these proteins to generate neutralizing antibodies against SARS-CoV-2. According to the high amount of binding antibody we achieved, we are confident to observe large number of neutralizing antibodies.”

Bioapp CEO Son Eun-joo said this was “the first case demonstrating the potential for the plant-based SARS-CoV-2 antigen proteins to become a vaccine in Korea.” Also stating, “The research team will evaluate the ability of protection against viral infection through a challenge test in animal models with ferrets (a mammal of the weasel family) and hamsters.”

Green bio-based COVID-19 vaccine is one of the most innovative attempt to conquer the challenge imposed by the pandemic with its advantage in reducing the vaccine development timeline up to 6 weeks (typically, vaccine development process with eggs could take up to 6 months), enabling quick response against emergent of possible mutations of viruses. Hence the global pharmaceutical companies’ green bio-based COVID-19 vaccine roundup began.

On July 7th, GSK, a frontrunner for the infectious disease area, announced the co-development collaboration with a Canadian green-vaccine developer, Medicago (a subsidiary of Mitsubishi Tanabe) for the development of plant-based COVID-19 vaccine. The type of vaccine involved in this collaboration is the same type of vaccine (plant-derived virus-like particle) currently under development by Hanmi Science and Bioapp.

The COVID MDT program has been accelerated further with the successful first animal study results along with synergistic effects between Hanmi’s experience in drug development and Bioapp’s state-of-the-art plant vaccine technology. Both companies proclaimed that they will make their best efforts to make Korea the leader in green bio.

식물에서 생산된 코로나19 항원 단백질의 백신 가능성에 대한 기대가 높아지고 있다.

한미사이언스와 바이오벤처 바이오앱은 현재 다양한 코로나19 식물 백신 후보 항원 단백질을 생산 중이며, 이를 이용한 마우스•기니피그 동물실험에서 높은 항체 반응을 확인했다고 9일 밝혔다.

이와 함께 김동민 조선의대 교수 연구팀도 바이오앱에서 생산한 항원과 큐라티스 사의 다양한 면역증강제를 활용해 마우스 2회 주사 면역 실험을 수행했다. 연구팀은 세포매개성 면역반응과 체액성 면역반응 활성화가 일어날 뿐 아니라, ELISA 방법으로 1만 6000배에서 양성 항체반응이 나타나는 것을 확인했다.

바이오앱은 "현재 코로나19 바이러스를 중화할 수 있는 '중화항체' 분석을 준비 중"이라며 "항체 수치로 볼 때 많은 양의 중화항체가 형성됐을 것으로 자신한다"고 말했다.

손은주 바이오앱 대표는 "식물에서 생산된 코로나19 항원 단백질의 백신 가능성을 입증한 첫번째 결과"라며 "연구팀은 이어서 페럿(족제비과의 포유류)과 햄스터 동물 모델을 이용한 공격접종 실험을 통해 바이러스 방어 효능을 분석할 예정"이라고 설명했다.

지난 7일 영국 GSK와 캐나다 식물백신회사 메디카고(미쓰비시다나베 자회사)가 발표한 식물 백신 개발 협력 내용과 한미사이언스•바이오앱이 공동 개발중인 식물 유래 VLP(Virus Like Particle)는 같은 백신 형태다.

메디카고 역시 전임상에서 높은 중화 항체 반응을 확인하고 곧장 임상1상에 돌입한다고 발표했으며, 백신을 만드는 기간을 6주 정도로 단축시켜(계란을 사용하는 백신개발 과정은 약 6개월 소요) 감염 바이러스의 변종이 나타나도 신속하게 대처할 수 있다고 설명했다.

한미의 축적된 제약 바이오 기술과 바이오앱의 혁신적인 식물 백신 기술로 융합된 Covid MDT 프로그램은 성공적인 첫번째 동물 실험과 GSK의 경쟁 참여로 더욱 가속화되고 있다.

한미사이언스와 바이오앱은 한국이 그린 바이오 선두주자가 되도록 최선을 다하겠다고 밝혔다.

출처: 의협신문

Deserts of the U.S. Southwest are extreme habitats for most plants, but, remarkably, microscopic green algae live there that are extraordinarily tolerant of dehydration. These tiny green algae (many just a few microns in size) live embedded in microbiotic soil crusts, which are characteristic of arid areas and are formed by communities of bacteria, lichens, microalgae, fungi, and even small mosses. After completely drying out, the algae can become active and start photosynthesizing again within seconds of receiving a drop of water.

How are they so resilient? That question is at the core of research by Elena Lopez Peredo and Zoe Cardon of the Marine Biological Laboratory (MBL), published this week in Proceedings of the National Academy of Sciences. Given the intensified droughts and altered precipitation patterns predicted as the global climate warms, understanding the adaptations that facilitate green plant survival in arid environments is pressing.

Working with two particularly resilient species of green microalgae (Acutodesmus deserticola and Flechtneria rotunda), Peredo and Cardon studied up- and down-regulation of gene expression during desiccation, and added a twist. They also analyzed gene expression in a close aquatic relative (Enallax costatus) as it dried out and ultimately died. Surprisingly, all three algae -- desiccation tolerant or not -- upregulated the expression of groups of genes known to protect even seed plants during drought. But the desiccation-tolerant algae also ramped down expression of genes coding for many other basic cellular processes, seemingly putting the brakes on their metabolism. The aquatic relative did not.

Peredo's and Cardon's research suggests this new perspective on desiccation tolerance warrants investigation in green plants more broadly. Upregulation of gene expression coding for protective proteins may be necessary but not sufficient; downregulation of diverse metabolic genes may also be key to survival.

Source: ScienceDaily

After several years of experimentation, scientists have engineered thale cress, or Arabidopsis thaliana, to behave like a succulent, improving water-use efficiency, salinity tolerance and reducing the effects of drought. The tissue succulence engineering method devised for this small flowering plant can be used in other plants to improve drought and salinity tolerance with the goal of moving this approach into food and bioenergy crops.

"Water-storing tissue is one of the most successful adaptations in plants that enables them to survive long periods of drought. This anatomical trait will become more important as global temperatures rise, increasing the magnitude and duration of drought events during the 21st century," said University of Nevada, Reno Biochemistry and Molecular Biology Professor John Cushman, co-author of a new scientific paper on plant tissue succulence published in the Plant Journal.

The work will be combined with another of Cushman's projects: engineering another trait called crassulacean acid metabolism (CAM), a water-conserving mode of photosynthesis that can be applied to plants to improve water-use efficiency.

"The two adaptations work hand-in-hand," Cushman, of the University's College of Agriculture, Biotechnology & Natural Resources, said. "Our overall goal is to engineer CAM, but in order to do this efficiently we needed to engineer a leaf anatomy that had larger cells to store malic acid that accumulates in the plant at night. An added bonus was that these larger cells also served to store water to overcome drought and to dilute salt and other ions taken up by the plant, making them more salt tolerant."

When a plant takes up carbon dioxide, it takes it through its pores on the leaf, called stomata. They open their stomata so carbon dioxide goes in, and then it gets fixed into sugars and all other compounds that support most of life on earth. But, when stomata open, not only does carbon dioxide come in, but also water vapor goes out, and because plants transpire to cool themselves, they lose enormous amounts of water."

Cushman's team of scientists created genetically modified A. thaliana with increased cell size resulting in larger plants with increased leaf thickness, more water-storage capacity, and fewer and less open stomatal pores to limit water loss from the leaf due to the overexpression of a gene, known as VvCEB1 to scientists. The gene is involved in the cell expansion phase of berry development in wine grapes.

The resulting tissue succulence serves two purposes.

"Larger cells have larger vacuoles to store malate at night, which serves as the carbon source for carbon dioxide release and refixation, by what's called Rubisco enzyme action, during the day behind closed stomatal pores, thereby limiting photorespiration and water loss" Cushman said. "And, the succulent tissue traps the carbon dioxide that is released during the day from the decarboxylation of malate so that it can be refixed more efficiently by Rubisco.

One of the major benefits of VvCEB1 gene overexpression was the observed improvements in whole-plant instantaneous and integrated water-use efficiency, which increased up to 2.6-fold and 2.3-fold, respectively. Water-use efficiency is the ratio of carbon fixed or biomass produced to the rate of transpiration or water loss by the plant. These improvements were correlated with the degree of leaf thickness and tissue succulence, as well as lower stomatal pore density and reduced pore openings.

"We tried a number of candidate genes, but we only observed this remarkable phenotype with the VvCEB1 gene," Cushman said. "We typically will survey between 10 to 30 independent transgenic lines, and then these are grown for two to three generations before detailed testing."

Arabidopsis thaliana is a powerful model for the study of growth and development processes in plants. It is a small weed-like plant that has a short generation time of about six weeks and grows well under laboratory conditions where it produces large amounts of seeds.

Engineered tissue succulence is expected to provide an effective strategy for improving water-use efficiency, drought avoidance or attenuation, salinity tolerance and for optimizing performance of CAM.

CAM plants are very smart, keeping their stomata closed during the day, and only opening them at night when evapotranspiration is low because it is cooler and the sun is not shining, Cushman explained. The significance of CAM is found in its unique ability to conserve water. Where most plants would take in carbon dioxide during the day, CAM plants do so at night.

"Essentially, CAM plants are five to six times more water-use efficient, whereas most plants are very water inefficient," he said. "The tissue succulence associated with CAM and other adaptive traits like thicker cuticles and the accumulation of epicuticular waxes, means that they can reduce leaf heating during the day by reflecting some of the light hitting the leaf. Many desert-adapted CAM plants also have a greater ability to tolerate high temperatures.

With demand for agricultural products expected to increase by as much as 70% to serve a growing human population, which is predicted to reach about 9.6 billion by 2050, Cushman and his team are pursuing these biotechnology solutions to address potential future food and bioenergy shortages.

"We plan to move both tissue succulence and CAM engineering into crop plants. This current work is proof-of-concept," Cushman said.

Source: PHYS

한미약품그룹 지주회사 한미사이언스는 바이오앱과 식물 기반 재조합 단백질 생산 플랫폼 기술을 활용한 다양한 신약개발 협력과 혁신적 바이오 생산 공법을 도입하는 내용의 MOU를 체결했다고 17일 밝혔다.

바이오앱은 포스텍 연구교수를 역임한 손은주 대표가 창업한 바이오벤처로, 식물 기반 단백질을 활용해 바이오 의약품을 개발 및 생산하는 기업이다. 포스코로부터 기술투자를 지원받고 있는 바이오앱은 경상북도 포항에 GMP 인증 백신 공장 및 연구소 등 제조•연구 시설을 구축했으며, 현재 자사 원천기술인 '그린백신'을 기반으로 코스닥 기술특례 상장을 추진하고 있다.

현재 바이오앱은 단백질 고발현 및 고효율 분리•정제 기술을 바탕으로 대량의 유용 단백질을 식물에서 생산할 수 있는 플랫폼을 구축했다. 또 나노미터 크기의 바이러스 유사입자(virus-like particle, VLP)를 식물에서 생산하는 그린나노 플랫폼 기술을 자체 개발해 약물전달체, 백신, 치료제 개발 등 다양한 분야에 접목을 시도하고 있다.

한미사이언스는 바이오앱의 기술력과 생산 공정에 주목해 최근 발표한 6대 비전 중 하나인 '그린 바이오'의 혁신을 현실화할 수 있을 것으로 기대하고 있다.

앞서 임종윤 한미사이언스 대표는 지난 15일 "사이디오 시그마'로 명명한 한미그룹 6대 비전을 발표한 바 있다.

한미사이언스는 이번 MOU를 토대로 바이오앱과 함께 코로나바이러스감염증-19(코로나19) 치료 및 예방을 위한 백신 개발에 나선다.

바이오앱 원천기술인 그린나노 플랫폼 기술을 활용하면 필요한 단백질 항원만을 분리정제해 코로나19 백신 개발에 적용할 수 있다는 게 한미 측 설명이다. 식물에서 분리정제한 재조합 단백질을 활용하기 때문에 부작용이 거의 없으면서도 효과는 우수하다는 장점이 있다.

이와 함께 한미사이언스는 바이오앱의 혁신적인 식물 기반 단백질 생산 공정에 주목하고 있다. 대규모 시설 구축이 필요한 기존의 바이오공장을 뛰어 넘는 혁신 생산 공법을 그린 바이오에서 찾겠다는 구상이다.

바이오의약품 개발에 필수적인 단백질은 박테리아나 효모, 곤충 세포, 포유류 세포, 형질전환 동물, 식물 일과성 발현, 유전자 이식 식물 등에서 얻을 수 있다. 바이오앱은 식물 일과성 발현 및 유전자 이식 식물 개발에 필요한 원천 기술을 보유한 기업이다.

무엇보다 밀폐형 식물공장 방식을 적용하면 비교적 단기간 내 제품 생산이 가능하다. 이 때문에 한미약품그룹은 미래의 혁신 가치로 개발 중인 다양한 바이오신약들의 대량 생산 적용에도 접목할 수 있을 것으로 예상하고 있다.

임종윤 한미사이언스 대표는 "기존 동물이나 미생물을 활용한 유전자 재조합 방식뿐 아니라 최근 새롭게 부각되고 있는 식물 기반 유전자 재조합 기술도 미래 한미약품그룹이 품어야 할 의미 있는 바이오 영역이며, 특히 그린 바이오 생성 공정을 도입하면 이 분야의 게임 체인저로 등극할 수 있을 것이란 기대고 갖고 있다"면서 "이번 MOU를 통해 6대 비전 중 하나인 그린 바이오 분야에서의 혁신을 이끌어 내겠다"고 밝혔다.

손은주 바이오앱 대표는 "식물생명공학 기술을 이용해 원헬스 이념을 구현하는 바이오앱과 글로벌 제약그룹인 한미사이언스가 협업하면 미래 신약 분야 패러다임을 전환시킬 것으로 확신한다"며 "바이오앱이 보유한 그린 바이오텍 플랫폼 기반 기술에 한미약품그룹의 제품화 역량을 동원해 지역 산업 발전에도 크게 기여할 것으로 기대한다"고 말했다.

출처: EBN

Breeding plants for specific characteristics goes back thousands of years. For most of that time, the process has been slow and tied to the agricultural cycle. Farmers identified plants with desirable traits, harvested seeds and hoped for a reprise of a specific trait in the next generation of seedlings. Gene editing made it possible to accelerate this process—to a point—but reliance on tissue culture, an expensive and time-consuming process, substantially limited innovation.

A study recently published in Nature Plants outlines a new approach that may significantly speed the development of new plant varieties by skipping tissue culture and boosting heritability. The technique, developed by Evan Ellison, a graduate student in the lab of Dan Voytas, a professor in the College of Biological Sciences' Department of Genetics, Cell Biology and Development, draws on the ability of RNA viruses to effectively deliver genetic information to plant cells. Ellison collaborated on the study with Voytas, a master's student in the Voytas lab, and colleagues at the University of California, Davis.

RNA viral vectors—natural viruses that are stripped down and disarmed before being repurposed—are one of several ways to deliver genetic information. Ellison's approach opens up a novel avenue for experimentation.

"Plant biology has a problem with scalability because you can only make changes to a few genes at a time," said Ellison. "This approach makes it easy to build these vectors and deliver them to plants, which means you can iterate dozens of times very quickly. It's cheaper, easier and less labor intensive."

Ellison turned to mobile RNA, or mobile motifs, that already exist in plants with an eye to making modifications more heritable.

"In plants you want to get as many cells edited as you can. I thought mobile motifs are kind of exactly what we want,'" he said, noting it underpins flowering and other critical functions and are adept at cell-to-cell movement. Because of this, Ellison thought it might be particularly good at delivering gene editing reagents to create edited plants more efficiently.

Results suggest that the gambit paid off. With the mobile motif for flowering, heritable editing frequency ranged from 65% to 100% of progeny, a considerable improvement on current rates of heritability in gene-edited plants created using other techniques.

"I was completely dumbfounded when Evan first showed me his data demonstrating such high frequencies of gene editing," said Voytas. "The next step is to enable his method in a wide variety of crop plants so we can fully capture the potential of plant gene editing for crop improvement."

출처: PHYS

이스라엘 바이오텍 프로탈릭스 바이오테라퓨틱스(Protalix BioTherapeutics)가 미국 식품의약국(FDA)에 희귀질환인 파브리병(Fabry disease) 치료제 후보물질에 대한 생물의약품 허가신청서(biologics license application, BLA)를 제출했다.

프로탈릭스는 동물세포보다 저렴하고, 상온에서 안정적으로 약물을 생산할 수 있는 장점을 가진 식물세포를 사용해 치료제를 개발 및 생산하는 회사다.

프로탈릭스는 지난달 28일(현지시간) 미국 FDA에 희귀 유전질환인 파브리병 치료제 후보물질 ‘PRX-102(pegunigalsidase alfa)’의 가속승인 절차를 위한 BLA를 제출했다고 밝혔다. 프로탈릭스는 2018년 FDA에서 PRX-102에 대해 패스트트랙으로 지정받은 바 있다. 프로탈릭스의 PRX-102는 키에지 그룹의 사업부문 중 하나인 키에지 국제 희귀질환(Chiesi global rare disease)과 공동개발한 약물이다.

파브리병(Fabry Disease)은 인구 4만~6만명당 한명에서 발병하는 X-염색체 연관 희귀 유전병으로 리소좀에 α-갈락토시다제-A 효소(α-Galactosidase-A enzyme)의 손상에 의해 유발된다. 파브리병은 신체 전반에 걸쳐 혈관벽에 Gb3(globotriaosylceramide)라는 지방 물질의 비정상적인 축적을 유발하고, 이로 인해 말초 감각의 손상과 통증에서부터 신장, 심장, 뇌 혈관 등의 장기 손상을 일으킨다.

프로탈릭스는 식물세포에서 생산한 단백질 약물에 대해 FDA에서 승인받은 첫 회사다. 프로탈릭스는 2012년 FDA에서 고셔병(Gaucher disease)에 대한 효소 교체요법(Enzyme Replace Therapy, ERT) 치료제로 당근세포(carrot cell)에서 만든 '엘레라이소(ELELYSO™, taliglucerase alfa)'를 승인받았다.

이번에 허가절차에 들어간 프로탈릭스의 ‘PRX-102’는 담배세포(tobacco cell)에서 생산한 약물로 α-갈락토시다제-A 효소의 페길화(PEGylation)을 통해 체내 안정성을 증가시킨 형태다. FDA에서 승인받으면 프로탈릭스의 두번째 식물세포 기반 약물이 된다.

드로르 바샨(Dror Bashan) 프로탈릭스 CEO는 “PRX-102를 가속승인 절차로 BLA를 제출할 수 있도록 도와준 FDA에 감사하다”며 “키에지와 함께 이번 마일스톤이 가능하게 해준 연구자들과 임상 참여자분들께 감사의 인사를 전한다”고 말했다.

PRX-102, 임상 3상에서 "eGFR, Gb3 수치 개선"

담배세포에서 생산한 PRX-102의 임상결과를 알아보자. 프로탈릭스는 파브리병을 앓고 있는 환자 22명을 대상으로 PRX-102의 임상 3상(NCT03018730)의 중간분석결과를 지난달 11일 발표한 바 있다. 프로탈릭스는 기존에 파브리병 치료제로 사용되는 다케다의 ‘레프라갈(Replagal, agalsidase alfa)’로 최소 2년간 치료 중인 환자를 모집해 PRX-102를 2주에 1회씩 12개월간 정맥투여했다.

프로탈릭스는 파브리병환자에게 PRX-102를 투여한 결과, 신장의 기능을 나타내는 연간 추정 사구체여과율(estimated glomerular filtration rate, eGFR) 평균 수치와 혈장내 Gb3 농도를 개선하고 안전성을 확인했다. 구체적으로 PRX-102를 투여한 남성환자의 경우 연간 eGFR수치가 -6.36mL/min/1.73m^2에서 -1.73mL/min/1.73m^2로, 여성환자의 경우 -5.03mL/min/1.73m^2에서 -0.21mL/min/1.73m^2로 개선됐다. 또, PRX-102는 혈장내 Gb3 농도를 남성환자와 여성환자에서 각각 51.81nM→19.55nM(32.35%), 13.81nM→4.57nM(29.81%)로 감소시켰다.

프로탈릭스는 PRX-102가 우수한 약물안전성을 보였다고 설명했다. 임상에 참여한 22명의 환자 중 2명은 과민반응으로 인해 약물 투여를 중단했으나, 20명은 12개월간의 치료를 마쳤다. 프로탈릭스는 임상을 마친 환자 중 18명은 장기간 임상연구로 전환해 PRX-102로 계속 치료하기로 결정했다고 밝혔다.

기존에 파브리병에 대해 승인받은 약물로는 사노피의 ‘파브라자임(Fabrazyme)’, 다케다의 ‘레프라갈(Replagal)’, 아미쿠스(Armicus)의 ‘갈라폴드(Galafold)’가 있다. 프로탈릭스의 PRX-102는 파브라자임, 레프라갈처럼 α-갈락토시다제-A 효소에 대한 효소교체요법(ERT) 방식의 치료제로 2주마다 병원을 방문해 정맥투여를 받아야 한다. 프로탈릭스는 현재 사노피의 파브라자임과 효과를 직접 비교(head to head)하는 임상 3상(NCT02795676)을 진행 중으로 2021년 중간 결과를 발표할 계획이다.

식물을 이용한 단백질 의약품 생산

식물세포에서 단백질 의약품을 생산하기 위해서는 먼저 식물에 원하는 단백질을 발현시켜야 한다. 이를 위해 일반적으로 아그로박테리움(agrobacterium)을 이용한다. 아그로박테리움은 식물의 형질전환에 사용해온 균주로 평상시엔 식물에 기생하면서 자기에게 필요한 영양분을 얻는다. 그러나 식물에 상처가 날 경우 아그로박테리움은 식물에 침투해 들어가 식물의 DNA를 조작한다. 이런 성질을 이용해 의약품으로 사용하기 위한 단백질을 암호화하는 DNA를 식물에 집어넣는다.

일반적으로 많이 사용하는 담배 식물은 성장 속도가 40일 정도로 빠르고 바이오매스가 많아 다른 식물에 비해 약물을 대량으로 만들 수 있다.

맵 바이오파마슈티컬(Mapp Biopharmaceutical)는 이런 특성을 이용해 담배식물인 니코티아나 벤타미아나(Nicotiana benthamiana)에서 만든 에볼라바이러스 중화항체 지맵(ZMapp)에 대해 2014년 FDA에서 치료제로 승인받았다.

프로탈릭스는 식물세포 배양를 통한 약물생산이 동물세포에 비해 여러 장점이 있다고 강조한다. 먼저, 동물세포보다 비용면에서 저렴하다. 동물세포를 사용해 생산하는 젠자임(Genzyme)의 고셔병치료제 ‘세레자임(Cerezyme, imiglucerase)’에 비해 프로탈릭스의 엘레라이소는 25% 저렴하다. 다음으로 인간에게 감염되는 바이러스의 오염(contamination)없이 상온에서 간단한 제조공정으로 약물을 생산할 수 있다. 동물세포를 사용할 경우 바이러스의 오염을 배제하기 위해 숙련된 기술자와 대규모 설비가 필요하다. 마지막으로 필요한 경우 신속하게 대량생산(horizontal scale-up)이 가능하다.

형질전환 식물을 만들거나 식물에 특정 유전자를 일시적으로 발현시켜 의약품을 생산하는 방식은 식물세포를 배양하는 방식에 비해 생산용량이 적고, 단백질 추출양이 적은 단점이 있으나 생산 절차가 간단하고 빠르며, 단백질의 분리 및 정제가 간단하고, 환경에 대한 규제가 적은 장점이 있다(doi: 10.4155/pbp.14.32). 이런 방식은 평상시에 기르고 있던 식물에 필요에 따라 유전자를 발현시켜 신속하게 의약품을 생산할 수 있다. 예를 들어 캐나다 메디카고(Medicago)는 평상시에 식물을 기르다가, 독감이나 기타 전염병이 대유행을 하게 될 경우 1주에 최대 150만도즈의 백신을 생산할 수 있다(doi: 10.1186/s13104-015-1157-1).

국내의 지플러스생명과학은 CRISPR 유전자 편집기술을 이용해 식물에서 면역 항암 바이오베터 의약품 개발을 진행하고 있다. 지플러스는 동물세포에서 생산되는 항체보다 효능은 높이고 부작용은 낮춘 항체 바이오베터를 식물에서 만들어, 저렴한 비용으로 고품질 의약품을 제공하는 것을 목표로 하고 있다.

출처: Bio Spectator

작년 말 중국에서 시작된 신종 코로나바이러스 감염증(코로나19)이 세계에 유행하면서 사람들의 일상을 바꿔놓고 있다. 코로나 바이러스는 일반적인 독감 바이러스와 비슷한 형태지만 아직 치료제와 백신이 없다. 한국을 포함해 미국 유럽 등 위기의식을 느낀 각국에서는 모든 역량과 자본을 코로나19 백신 개발에 집중하고 있다. 언제까지 기다려야 할까. 백신은 개발 속도가 느리고 바이러스는 백신 개발도 어렵다고 하는데 그 이유는 무엇일까.

변이 많을수록 백신 개발 힘들어

인체는 바이러스, 세균 등 자신과 다른 단백질을 가지고 있는 물질이 외부에서 체내로 들어오면 이를 인식한 뒤 제거하는 시스템을 갖추고 있다. 백신은 인체가 인식할 수 있는 바이러스와 세균의 단백질에서 질병을 유발하는 부분은 제거한 물질을 가리킨다. 백신이 몸에 들어오면 면역체계는 바이러스나 세균이 들어왔다고 인식하고 이에 저항할 수 있는 시스템을 구축한다. 향후 진짜 바이러스와 세균이 침투했을 때 방어막 역할을 한다.

백신 개발의 관건은 바이러스와 세균의 단백질 중 어느 부분을 이용할지 결정하는 것이다. 변이가 쉽게 일어나는 바이러스의 백신을 개발하는 게 어려운 이유는 단백질의 모양이 변이에 의해 쉽게 바뀌기 때문이다. 바이러스의 단백질 종류와 구조를 알고 어떤 특정한 단백질을 백신으로 개발했다고 하자. 처음에는 효과가 있겠지만 바이러스가 변이를 일으켜 해당 단백질의 모양이 바뀔 수 있다. 대개 백신으로 이용하는 단백질은 우리 몸에 문제를 발생시키면 안 되기 때문에 별다른 기능이 없고 단순히 바이러스의 모양을 유지하기 위해 존재하는 부분인 경우가 많다. 이 부분은 바이러스가 변이를 일으켜도 바이러스의 원래 기능에는 크게 문제가 생기지 않기 때문에 쉽게 변이가 일어날 수 있다. 따라서 안정적인 백신을 개발하려면 변이가 생기기 어려운 단백질을 찾아내거나 바이러스의 기능에 중요하지만 인체에 큰 영향이 없는 부분을 찾아내야 한다. 변이가 심할수록 백신 개발이 어려운 이유다.

박테리아•식물로 백신 생산

백신을 개발했다면 이를 대량 생산해 세계에 보급하는 것이 다음 과제다. DNA 구조가 밝혀지고 과학기술이 발전하면서 우리가 원하는 대로 유전자를 재조합할 수 있는 기술이 개발됐다. 이제 우리는 백신의 DNA를 재조합, 다양한 생물을 이용해 백신을 생산할 수 있는 기술이 있다. 대표적인 예가 박테리아다. 백신을 만들 수 있는 ‘지도’인 DNA를 박테리아에 넣어주고 박테리아를 잘 키워서 양을 늘리는 것이다. 그러면 박테리아가 알아서 DNA를 보고 백신을 생산해 자신의 몸속에 쌓아놓는다. 우리는 일정 시간이 지난 뒤 박테리아를 파괴하고 속에 든 단백질(백신)만 쏙 빼내면 된다.

여기에 문제가 없는 것은 아니다. 박테리아를 파괴하고 그 속에 들어 있는 백신만 잘 골라내는 작업은 쉽지 않다. 게다가 박테리아에는 독성물질이 많다. 백신을 골라내는 과정에서 독성물질이 남아 있다면 인체에 투여할 수 없기 때문에 세심한 노력이 필요하다. 비용 부담도 발생하기 마련이다.

모든 생물은 자신의 몸속에서 만들어진 단백질에 일종의 ‘표시’를 해 둔다. 이 표시는 생물마다 다른데 문제는 표시에 의해 단백질의 기능이 바뀔 수 있다는 것이다. 같은 백신이라도 어떤 생물을 이용해서 만드느냐에 따라 그 기능에 크게 차이가 날 수 있다. 최근 박테리아가 아닌 식물에서 백신을 생산하려는 노력이 이뤄지는 배경이다. 식물은 박테리아와 달리 인간에게 악영향을 미칠 위험이 상대적으로 작고 생산 비용이 저렴하다. 미국 바이오기업 맵바이오파마수티컬은 에볼라 백신을 식물에서 추출해 상용화했다. 백신을 생산할 수 있는 생물을 박테리아와 식물 두 종류 모두에서 확보하고 있다면 백신을 생산하기가 훨씬 유리해질 것이다.

식물 기반의 전염병 대응 모델 필요

박테리아는 많은 영양분이 들어 있는 물(배지)에서 자란다. 이 때문에 대량 생산하려면 거대한 수조가 필요하다. 대용량 배지에서 박테리아를 분리 및 정제하려면 추가 시설이 필요하다. 지금처럼 전염병이 크게 유행할 때 박테리아를 이용해 백신을 생산하려면 시간과 비용이 많이 든다.

백신 생산이 가능한 식물이 있다면 이야기가 달라진다. 이 백신의 DNA를 가지고 있는 식물을 잘 키워서 씨앗을 대량으로 확보해 놓으면 된다. 씨앗은 장기간 보관이 가능하며 부피도 작아 얼마든지 많은 양을 확보해 놓을 수 있다. 만약 전염병이 빠르게 퍼질 경우 씨앗을 뿌려 식물을 땅에서 키운 뒤 한두 달 뒤에 잎을 수확해 백신을 뽑아낼 수 있다. 박테리아 기반 생산보다 훨씬 빠르고 간편하다. 식물에서 백신을 발현시켜 약으로 사용하는 것이야말로 일반적인 식물을 약초(藥草)로 바꾸는 일이 아닐까.

출처: 한경헬스

21세기 기후변화는 물부족, 식량부족, 석유고갈, 환경오염 등 우리들에게 많은 과제를 남겨놓고 있다. 결국 인류는 이런 과제를 해결하지 않고는 생존하여 나갈 수 없기 때문에 유엔을 중심으로 세계 각국들은 매년 기후변화 정상회담을 통하여 그 대안을 논의하고 있는 것이다. 따라서 많은 전문가들은 이를 뒷받침해 나갈 수 있는 기후산업이 앞으로 각광을 받는 첨단산업으로 등장하게 될 것이라고 전망하고 있다.

기후산업은 토지를 이용하는 농업이 핵심 주체가 되기 때문에 이를 신 농업산업이라고도 부른다. 즉 염분에 강한 작물을 개발하여 2020년 보편화될 것으로 예상되는 해수농업은 물부족과 식량부족을 해결해 낼 것이다.

미세 해조류인 앨지(algae)를 배양하는 앨지 산업은 제3세대 바이오 에너지를 대량생산하여 석유고갈문제를 해결해 낼 것이다. 그리고 세포공학기술을 이용하여 쇠고기의 세포를 육류로 배양한 뒤 가공 처리하여 육류를 원하는 크기나 모양으로 배양하는 배양육산업은 환경오염을 감축시켜 나갈 수 있게 될 것이다.

이밖에 IT를 활용한 무인 해충예찰 시스템은 덫에 걸린 해충의 이미지를 분석해 해충의 종류와 발생 시기, 밀도를 파악해 방제 적기를 휴대전화 문자메시지로 전송해주게 될 것이다. BT는 신품종 개발, 기능성물질 생산, 동물복제, 생물농약 개발 등으로 활용되어 인체 질병 치료용 동물 개발이 가능케 할 것이다.

국내에서는 장기를 인체에 이식해도 거부반응이 없는 미니돼지가 개발 중이다. 신소재기술은 농기계나 유리온실의 경량화에 쓰이고 있고 환경기술은 농업의 환경오염을 최소화하고, 에너지 기술은 에너지 절약형 농업을 발전시키고 있다.

이제 농업은 첨단과학이 집약돼 있는 산업으로 먹거리를 생산만 하던 시대는 흘러간 지 오래다. 더 많이, 더 맛있게, 더 안전하게 생산하는 것은 기본으로 화석연료를 바이오에너지가 대체하고, 빌딩형 작물생산 공장시스템이 개발돼 도심에서도 식물을 길러낸다. 누에고치로 인공 고막과 뼈를 만들고, 사람에게 장기를 공급하기 위한 맞춤형 동물도 생산된다.

첫째, 물 부족과 식량부족을 해결해 줄 해수농업

인간을 포함한 아주 많은 생명체는 비, 강, 호수, 샘, 냇물들로부터의 담수를 통해 자라나는 작물들에 의존한다. 특히 인간이 가장 많이 소비하는 다섯 가지 작물인 밀, 옥수수, 쌀, 감자, 그리고 대두는 모두 소금을 견뎌내지 못하는 작물들이다.

유엔 식량농업기구는 향후 30년 동안 열대와 아열대 지방의 증가하는 인구를 부양하기 위해 약 2억 헥타르 (약 4억 9420만 에이커)의 새로운 경작지가 필요할 것으로 전망하고 있다. 그렇지만 해수에 내성이 강한 작물을 바닷물로 농사를 짓을 수 있다면 이를 해결할 수 있을 것이다. 이런 해수농업은 2020년부터 시작되어 2050년에는 바닷물로 농사를 짓는 일은 보편화될 전망이다.

해수농업이란 소금에 내성이 있는 작물들을 바다에서 끌어온 물을 통해 경작하는 것으로 사막 환경의 모래가 많은 토양에서는 가능하다는 것을 발견하였다. 그래서 지구상의 97%의 물은 바다에 존재하기 때문에 해수를 사용할 수 있다면 물 부족문제는 자연히 해결된다. 그리고 식량부족 문제도 지구 지면의 약 43%는 건조하거나 반건조한 땅으로 이루어져 있기 때문에 해수농업이 가능하다면 충분한 식량 확보도 가능한 일이다.

둘째, 석유고갈문제를 해결해 나갈 앨지(algae)산업

세계 각국들은 석유고갈에 대비하여 대체에너지 개발이 경쟁적으로 활발하게 일어나고 있다. 태양에너지, 풍력발전, 조력발전 등 신재생에너지가 각광을 받고 있지만 석유고갈을 대체할 만큼의 대량생산이 불가능하고 생산비용도 많이 들어 한계에 부닥치고 있다. 그렇지만 식물을 이용하는 바이오 연료 시장이 이에 대한 대안으로 제시되고 있다. 즉 세계 바이오 연료 시장은 현재 1세대인 곡물계에서 2세대인 목질계로 전환중이다. 그렇지만 바다의 미세조류계(algae)를 이용하는 3세대 바이오에너지가 본격화된다면 대량생산이 가능해져 석유의 대체에너지로서 역할을 담당하게 될 것이다.

이는 곡물연료보다 단위 면적당 300배 더 많은 연료생산이 가능하며 수확기간도 10일 이내로 단축되어 무한한 가능성을 보여주고 있다. 따라서 해조류를 이용한 앨지 산업은 석유고갈을 해결해 줄 대체에너지로 각광을 받게 되어 향후 세계경제를 지배하게 될 것이다. 우리나라는 삼면이 바다로 둘러쌓여 앨지(algae)산업의 최적지로 알려지고 있다.

셋째, 무공해 식품을 양산할 수 있는 식물공장

식물공장은 일정한 시설 내에서 빛, 온도, 습도, 이산화탄소 농도, 배양액 등의 환경조건을 인공적으로 제어해 계절이나 장소에 관계없이 자동으로 식물을 연속 생산하는 시스템이다.

식물공장은 파종에서부터 포장에 이르기까지 전 공정을 자동화해 최적의 생산 환경을 조성하기 때문에 농산물의 품질이 우수하다. 병해충을 원천적으로 차단하므로 화학농약을 사용할 필요가 없어 친환경 안전 농산물을 생산할 수 있다.

대도시 등 소비시장과 인접한 위치에 자리 잡게 되면 수송거리가 짧아져 유통비용을 절감할 수 있고 신선도 유지도 쉬워진다. 소비시장의 변화에 민첩하게 대응할 수 있으며, 시장 상황에 따라 상대적으로 유리한 품목으로 생산을 변경하거나 출하시기와 양을 조절하기가 쉽다.

일본은 이미 전국에 50여개의 식물공장을 만들었으며, 3년 내에 150개로 늘릴 계획이다. 시장에 유통되는 양상추의 1% 정도가 식물공장에서 생산되는 것으로 알려졌다. 일본 정부는 2020년까지 식물공장시장이 연간 5천억원 이상 규모로 확대될 전망이다. 최근 주목받는 빌딩형 식물공장(수직농장)은 프랑스, 미국, 덴마크, 캐나다 등 농업선진국에서도 각광을 받고 있다.

우리나라도 농업진흥청에서 현재 식물공장시스템의 시험장을 운영하고 있으며, 일부 농가와 현장에 기술 보급을 추진하고 있다. 강원도 철원군의 한 농가는 농진청의 인삼 수경재배 기술을 전수받아 대량생산에 돌입했고, 단국대의 한 벤처 농기업은 소규모 식물공장에서 수경재배한 양상추를 시판하고 있다. 식물공장과 관련한 국내 기술은 세계 최고 수준 대비 50% 정도로 평가받고 있으며 앞으로 무공해 식품을 제공할 수 있는 방안으로 기대된다.

넷째, 장기이식용 돼지 양육

우리나라는 1만 8,000명 정도가 장기이식을 기다리는 환자가 있지만 실제로 다른 사람의 장기를 이식받는 경우는 10%에 불과한 것으로 알려져 있다. 그렇지만 장기이식용 복제 무균돼지 ‘지노’가 태어났기 때문에 이를 해결해 나갈 수 있게 될 것이다.

미국에 이어 세계에서 두 번째로 개발한 지노는 장기가 손상된 인간에게 대체 장기를 제공할 수 있는 미니돼지다. 이종(異種) 간 장기 이식을 할 때 나타나는 초급성 거부반응 유전자를 제거되어 면역거부반응을 최소화할 수 있게 되었다고 한다. 국내 연구진은 우선 당뇨병 치료를 위한 췌장 이식에 이어 심장, 신장, 폐 등에 대한 이종 간 이식이 가능해 질 전망이다.

다섯째, 가축 이용 바이오신약 생산

서울대 한재용 교수팀은 세계 최초로 질병저항성 닭을 개발하였다. 이는 유전자 혼재기술을 이용한 것으로 앞으로 고성장, 기능성물질 함유, 난치병 치료 생리활성물질 생산, 첨단의료연구용 모델동물 등 다양한 형질전환 동물의 대량생산이 가능해진다.

최근 농촌진흥청은 인체 생리활성을 가진 단백질을 다량 함유한 달걀을 생산하는 닭 개발에 성공했다. 현재 국내 제약업체들은 복제돼지 젖을 통해 빈혈치료제(EPO)를 대량 추출하는 연구를 하고 있다. EPO는 사람의 신장에서 주로 생성되는 물질로 적혈구 생성을 돕기 때문에 빈혈치료제로 각광받고 있다. 그렇지만 추출량이 적어 1g에 60만 달러에 달할 만큼 값이 비싸다. EPO 대량 추출 연구가 성공할 경우 이론적으로 수유기의 돼지 한 마리에서 1㎏의 EPO를 생산할 수 있게 돼 말 그대로 ‘황금돼지’가 탄생하는 셈이다.

여섯째, 비타민A가 대량으로 함유된 황금쌀

유전자 분리의 신기술을 통해 성인병에 탁월한 각종 비타민, 지방산, 폴리페놀 등 기능성 성분이 다량 함유된 쌀, 콩, 배추, 고추, 들깨 등을 생산할 수 있는 시대가 됐다. 이는 평소 식생활만으로도 각종 질병을 예방하거나 치료제까지 식품으로 섭취할 수 있도록 하는 분자농업(molecular farming) 시대가 이미 도래 했다는 것이다.

첨단 생명공학 기술을 이용한 신물질, 신소재 가운데 최근 가장 눈에 띄는 것은 야맹증 등을 예방하는 비타민A를 만들어내는 황금 쌀이다. 2000년 비타민A 전구체(선행물질)인 베타카로틴을 생성하는 황금 쌀이 처음 개발됐다.

어린이 두뇌 발달을 촉진하는 오메가3 지방산을 만들어내는 콩도 개발되고 고등어 같은 등 푸른 생선 류에서 주로 얻어지는 DHA, EPA 등의 오메가3 지방산도 개발되어 성인들의 심장질환과 성장기 어린이의 두뇌 발달에 좋은 영향을 미칠 것이다.

이와 같이 21세기의 농업은 식량을 생산하던 과거의 농사방식에서 벗어나 기후변화에 따른 물부족, 식량부족, 석유고갈, 환경오염 등 문제를 해결해 나가는 신농업혁명이 일어나고 있다. 우리나라 농촌경제도 이런 추세에 발맞추어 신농업방식에서 가장 전망이 밝은 분야를 선정하여 발전의 발판을 마련하는 중장기 프로그램을 마련하여 획기적으로 농촌경제를 되살려내야 할 것이다.

출처: 브릿지경제

포항공과대학교(포스텍) 창업 벤처 바이오앱은 세계 최초로 식물 기반의 돼지열병 그린마커백신을 개발, 농림축산검역본부로부터 품목 허가를 받은 기업이다. 식물 단백질 고발현 및 분리 정제 관련 원천 기술을 갖고 있다.

회사 측은 "바이오앱의 원천 기술을 활용해 국가기관과 돼지열병 백신 관련 공동 연구를 진행했다"며 "안전한 단백질 성분의 백신을 개발해 '돼지열병 청정화'를 이루고자 했다"고 말했다. 이어 "현재 동물용 백신뿐 아니라 지카바이러스, 코로나19 등의 그린백신을 개발 중"이라며 "진단 키트에 필수적인 단백질성 바이오 소재 생산 분야로도 사업을 확대하고 있다"고 덧붙였다.

바이오앱의 주요 기술은 식물을 이용한 단백질 고발현•분리 정제 역량이다. 이 기술로 다양한 종류의 단백질을 신속히 대량 생산하고 있다. 회사에 따르면 황열 항체 진단키트의 핵심 소재인 항원 단백질을 식물 세포에서 추출해 3억원의 판매 실적을 낸 바 있다. 유전자 중합효소도 같은 방식으로 추출해 활성을 확인했다고 회사 측은 말했다.

바이오앱에 따르면 이 기술로 코로나19의 항원 단백질도 생산할 수 있다. 바이오앱 측은 "바이러스 표면의 스파이크 단백질은 항체 검사 타깃 단백질"이라며 "당이 많이 붙어 있는 당단백질 종류"라고 했다. 이어 "당화 작용이 활발한 식물에서 이 항원 단백질을 생산할 수 있다"며 "특히 식물 소포체 내에서 단백질과 같은 당패턴을 만들 수 있다"고 덧붙였다.

회사 측은 "바이오앱은 단백질 타깃팅 기술도 보유하고 있다"면서 "이 기술을 활용해 식물 세포 내 단백질을 소기관으로 이동시켜 품질을 높일 수 있다"고 했다. 이어 "식물 발현 시스템은 일시적 발현이 가능하고 대량 생산이 쉽다는 게 특징"이라면서 "현재 다양한 스파이크 항원 단백질을 개발 중이며 해외 수출 기회도 노리고 있다"고 덧붙였다.

이처럼 바이오앱은 식물 세포 내 단백질의 생산•이동•분해 관련 연구 분야에서 업계 수위 기업이다. 식물 세포 내 다양한 소기관으로 단백질을 이동, 효율 검증을 거쳐 고품질의 단백질 의약품을 개발할 수 있는 역량을 갖췄다는 게 회사 측 설명이다.

출처: 머니투데이