Category Archives: Genetic Engineering

The new facility will have a 200,000-liter production capacity and expanded R&D operations, and should be operational by the end of the year, said the company, which said its existing pilot facility will subsequently be converted to support the commercial production of a separate (undisclosed) high-value product that is currently undergoing product testing.

Provectus expects further expansion in the near term with plans for a supplementary 1 million liter facility already underway to support the commercialization of multiple products already in the pipeline, said founder and CEO Nusqe Spanton,who is based in Queensland, Australia, but is targeting the US, Europe, and Asia.

This is just the tip of the iceberg for Provectus Algae. The stage of development we are now at with our production platform gives us a clear line of sight to deliver some really exciting products to the food and beverage marketplace.

Speaking to FoodNavigator-USA in July, he said: "We don't see ourselves as a competitor to anyone[growing things like spirulina or astaxanthin in outdoor ponds, or chlorella for protein, orSchizochytriumsp forDHA omega-3s].We're a complementary platform, to deliver novel products in algae that has never been utilizedcommercially before.

He added: Were seeing huge interest from corporates; there's a significant move within the industry to move towards more sustainable and environmentally friendly production systems and alleviate some of the pain points associated with specialty food and beverage ingredients.

Provectus deploys a couple of approaches: the first uses algae species that naturally produce a given compound such as a pigment or fatty acid.

Here, deploying what it calls precision photosynthesis, Provectus can optimize and improve the algaes productivity by exposing it to light, which effectively alters its DNA and improves its productivity without using techniques that would be classified as genetic engineering from a regulatory perspective, said Spanton.

If we can control the light, we can control the DNA, and were able to deliver any type of light in the visible spectrum but also in the infrared and UV spectrum, manipulate the algae and push it down a metabolic pathway to vastly increase the production of a target substance naturally inside the algae."

The second approach involves using the entire synthetic biology toolkit, such as CRISPR [gene editing],insertion of genes, design and synthesis of DNA, and inserting those genes into the algae, and we can then use that to upregulate[the production of a given substance]or to produce products that aren't naturally occurring at all in the algae, he added.

We have the capability to do both naturally occurring products in novel algae species that have never been commercially grown before, and also biosynthetic products using our synthetic biology toolkit to design and engineer new algae strains for novel high performance productsthat don't exist today.

Read our recent interview with Spanton:If we can control the light, we can control the DNA Provectus Algae unlocks algaes potential as an industrial platform for high-value ingredients

See the article here:
Provectus Algae to start producing 'high-performance' red food coloring from algae to support the alternative protein market - FoodNavigator-USA.com

The British government has granted permission for a series of field trials of gene edited wheat for the first time in Europe, marking a significant move away from the EUs stance on the matter.

After the green light from the Department of Environment, Food and Rural Affairs (DEFRA), trials will be carried out by Rothamsted Research institute, a pioneer of GM crop trials since the 1990s, involving a genetically altered wheat created via the gene editing tool CRISPR.

The Hertfordshire-based experiments will be the first field trials of CRISPR edited wheat anywhere in the UK or Europe.

This technique is designed to introduce small changes to a targeted gene. Although it has been heralded by industry players as game-changing, the use of CRISPR technology remains controversial among other quarters.

A landmark European Court of Justice (ECJ) ruling in 2018 concluded that organisms obtained by new genomic techniques (NGTs), such as CRISPR, should, in principle, fall under the GMO Directive.

However, since leaving the bloc, the UK has signalled a step away from this ruling after England launched a consultation on gene editing in a bid to unlock substantial benefits for the sector and the environment.

The aim of the new field trials is to produce wheat that is low in the naturally occurring amino acid asparagine, which is converted to the carcinogenic processing contaminant, acrylamide, when bread is baked or toasted.

Acrylamide has been a very serious problem for food manufacturers since being discovered in food in 2002, according to project leader Professor Nigel Halford, pointing to the fact that it causes cancer in rodents and is considered probably carcinogenic for humans.

The cancer causing substance is also present in other wheat products and many crop-derived foods that are fried, baked, roasted or toasted, including crisps and other snacks, chips, roast potatoes and coffee.

By lowering the levels of asparagine in wheat, researchers hope to benefit both consumers, by reducing their exposure to acrylamide from their diet, and food businesses, by enabling them to comply with regulations on the presence of acrylamide in their products.

The move came under criticism from environmental campaigners, who warned that the aim of the project was too trivial compared to the risks carried by planting experimental genetically modified crops.

[The] UK Government decides the scourge of burnt toast is good enough reason to plant highly experimental GMO wheat in an open field, despite large numbers of public objections and Cancer Research UK advice that burnt food is not a cancer risk, anti-GM campaign group, GM Freeze, criticised on Twitter.

The news comes as the debate over the future of gene edited products heats up in the EU following the publication of the Commissions long awaited study on new genomic techniques.

The study, which was published in April, concluded that the current legal framework governing new genomic techniques (NGTs) is insufficient and indicated that new policy instruments should be considered to reap the benefits of this technology.

EU stakeholders have previously warned that any divergence from the EU on this matter risks the future of the UK-EU agrifood trading relationship.

Pekka Pesonen, secretary-general of farmers association COPA-COGECA, told EURACTIV back in January that such a move would be prohibitive in trading relations and that he was afraid that there would be no way to settle this without a level playing field on both sides of the Channel.

Likewise, the verdict is out as to whether consumers have an appetite for GE food.

Martin Husling, agriculture spokesman for the Greens/EFA in the European Parliament, previously told EURACTIV that consumer studies have demonstrated again and again that consumers do not want GM-food and feed.

The UK will, therefore, lose a big market for its gene-manipulated products, he warned, stressing that European products have a very good international reputation, partly because they are free of genetic engineering.

The project is planned to run over the next five years, ending in 2026, with plants being sown in September and October each year and harvested the following September.

Funding is in place for the first year, and additional support is being sought for the subsequent years.

[Edited by Josie Le Blond]

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First gene edited 'cancer-cutting' wheat trials get the go ahead in UK - EURACTIV

Thirty years ago, the legendary Walter Cronkite and world-renowned experts at ACSH took on the overblown fears of the day inBig Fears, Little Risks. In the wake of a pandemic thats claimed millions of lives, the documentary has been relaunched as a series tackling the fear-mongering surrounding GMOs, pesticides, vaccines, and nuclear power.

Matty Cardarople(Stranger Things) hosts some of the worlds leading scientists,including Dr. Bruce Ames and Dr. Paul Offit, as they give viewers a crash course on these wrongly vilified technologies. The take-home message: technological innovation offers us the best chance of ending a global health crisis, feeding the world, and reversing climate change.

On this episode of the Science Facts and Fallacies podcast, ACSH director of bio-sciencesCameron English chats with director Azel James and host Matty Cardarople about the films message, production, and September 8 premiere in Hollywood. Listen to the interview on iTunes, Spotify or at the Genetic Literacy Project. Follow@BigFearsIncon Twitter for updates.

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Podcast: ACSH Documentary 'Big Fears, Little Risks' Debuts Next Week In Hollywood - American Council on Science and Health

MIT engineers, in collaboration with scientists from Brigham and Womens Hospital and Novo Nordisk, are developing a drug capsule technology that could allow the oral delivery of monoclonal antibodies, or other large protein-based drugs that normally have to be injected, for diseases ranging from cancer, to rheumatoid arthritis, to Crohns disease. The new technology is a type of self-injecting capsule, called a liquid-injecting self-orienting millimeter-scale applicator (L-SOMA), which is swallowed, and then effectively injects the liquid medication directly into the stomach wall. In large animal preclinical models, investigators used the technology to deliver four commonly injected medications, including a monoclonal antibody.

Although it is still early days, we believe this device has the potential to transform treatment regimens across a range of therapeutic areas, said Ulrik Rahbek, vp at Novo Nordisk, who, together with Giovanni Traverso, PhD, the Karl van Tassel career development assistant professor of mechanical engineering at MIT and a gastroenterologist at Brigham and Womens Hospital, is co-senior author of the teams published paper in Nature Biotechnology. The ongoing research and development of this approach mean that several drugs that can currently only be administered via parenteral injections (non-oral routes) might be administered orally in the future. Our aim is to get the device into clinical trials as soon as possible, Rahbek noted.

The new L-SOMA technology is described in a paper titled, Oral delivery of systemic monoclonal antibodies, peptides, and small molecules using gastric auto-injectors.

While oral drug delivery is a simple, noninvasive way for patients to take their medicines, most large protein drugs cant be given orally because enzymes in the digestive tract break them down before they can be absorbed. This means that monoclonal antibody therapeutics, and other biologic drugs commonly have to be injected, which isnt so convenient, the authors noted. Oral administration provides a simple and noninvasive approach for drug delivery. However, due to poor absorption and swift enzymatic degradation in the gastrointestinal tract, a wide range of molecules must be parenterally injected to attain required doses and pharmacokinetics their injection-based method of administration often causes healthcare professionals to delay their initiation in favor of less effective oral medications. And patients themselves generally prefer pills, and say their quality of life can be affected when they are prescribed an injectable medication.

Although new technologies for oral delivery of biologic drugs are in development, they have their limitations, which means that they cant be used for some widely used biologics, such as pre-prandial insulin. We recognize today that pills are the preferred route of drug administration, not only for patients, but also for health care providers, Traverso said. If we can make it easier for patients to take their medication, then it is more likely that they will take it, and healthcare providers will be more likely to adopt therapies that are known to be effective Our group focuses on developing systems that make it easier for patients to receive their medications.

Traverso and colleagues have been working on different strategies to deliver biologic drugs orally. In 2019, they developed a capsule that could be used to inject up to 300 g of insulin. The pill, about the size of a blueberry, has a high, steep dome inspired by the leopard tortoise. Just as the tortoise is able to right itself if it rolls onto its back, the capsule is able to orient itself so that its needle can be injected into the lining of the stomach. In theoriginal version, the tip of the needle was made of compressed insulin, which dissolved in the tissue after being injected into the stomach wall.

The new L-SOMS technology described in theNature Biotechnology report maintains the same shape, allowing the capsule to orient itself correctly once it arrives in the stomach. However, the researchers redesigned the capsule interior so that it could be used to deliver liquid drugs, and in larger quantitiesup to 4 mg. This contrasts with their original version, the SOMA, which injects solid medications, but does not work with liquid drugs.

The L-SOMA technology would allow the delivery of liquid medications that need to be absorbed more quickly, or that are challenging to formulate as solids. Delivering drugs in liquid form can also help them to reach the bloodstream more rapidly, which is necessary for drugs like insulin and epinephrine, which is used to treat allergic responses.

The researchers designed their device to target the stomach, rather than later parts of the digestive tract, because the amount of time it takes for something to reach the stomach after being swallowed is fairly uniform from person to person, Traverso suggested. Also, the lining of the stomach is thick and muscular, making it possible to inject drugs while mitigating harmful side effects.

We recognized the potential of liquid injections to readily distribute within the stomachs submucosal plane, thereby accommodating larger dosing volumes than solid dosage forms, the authors commented. Additionally, the increased surface area of interaction between the formulation and the tissuewhen compared to a solid-dose pellet enables accelerated drug pharmacokinetics and pharmacodynamics. Moreover, by targeting the stomach rather than the small intestine, the capsule circumvents the 14 h required for gastric emptying.

The new delivery capsule is filled with fluid and also contains an injection needle and a plunger that helps to push the fluid out of the capsule. Both the needle and plunger are held in place by a pellet made of solid sugar. When the capsule enters the stomach, the humid environment causes the pellet to dissolve, pushing the needle into the stomach lining, while the plunger pushes the liquid through the needle. When the capsule is empty, a second plunger pulls the needle back into the capsule so that it can be safely excreted through the digestive tract.

To evaluate the pills efficacy, researchers tested the L-SOMA devices in pigs, dosing each with one of four treatments, including insulin, epinephrine, adalimumab (a monoclonal antibody used to treat rheumatoid arthritis, Crohns disease, and other autoimmune diseases), and a semaglutide-like GLP-1 analog (an anti-diabetic medication). They then collected blood samples from each of the animals and found that the L-SOMA pill delivered medications at comparable levels to those given with an injection. Delivery of monoclonal antibodies orally is one of the biggest challenges we face in the field of drug delivery science, Traverso said. From an engineering perspective, the ability to deliver monoclonal antibodies at significant levels really transforms how we start to think about the management of these conditions.

They also found that repeated treatments with the L-SOMA dosed with insulin induced the same results, suggesting it may be effective to give multiple, subsequent doses using L-SOMA. The pill achieves a maximum drug plasma concentration similar in magnitude to the standard-of-care subcutaneous injection as quickly as 30 min after dosing and delivers with a calculated absolute bioavailability of up to 80% within a timespan of hours, the team continued. They also found no signs of damage to the stomach lining following the injections, which penetrate about 4.5 mm into the tissue.

The MIT team is now working with Novo Nordisk to further develop the system. Going forward with a view to human testing, the researchers acknowledged that significant clinical development will be required to evaluate safety and effectiveness. Nevertheless, they concluded, These multi-day dosing experiments and oral administration in awake animal models support the translational potential of the system Here we show that the L-SOMA can carry and deliver a broad range of drugs across a range of molecular weights via an oral capsule. In doing so, it can provide a less intrusive route of administration for drugs that are otherwise limited to injectables.

The investigators anticipate that in the future, patients may be able to orally take a diverse array of medications that were once only available via needle. Additionally, because of the L-SOMAs injectable nature, scientists believe that it has the potential to administer vaccines, including the COVID-19 vaccine as well as potentially others.

Traverso and his collaborators continue to explore whats possible with the device. Through the application of fundamental engineering, the type of drugs we can deliver orally is being transformed, Traverso said. It changes how we think about managing different conditions. This technological advancement could apply to chronic conditions that require regular dosing or to systems that are more episodic. Mass administration of an otherwise injectable drug also becomes much easier if it can be given orally.

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Self-Injecting Pill Could Allow Oral Delivery of Monoclonal Antibody and Other Protein Drugs - Genetic Engineering & Biotechnology News

Encouraging data confirming activity in a solid tumor indication presented on first nine patients at low dose cohorts in ongoing autologous CAR-T trial in metastatic castrate-resistant prostate cancer

Three patients showed a greater than 50% decline in prostate-specific antigen (PSA) and concordant PSMA-PET imaging results, including one patient at lowest dose with evidence of complete tumor elimination

Favorable safety profile with modest overall rates of CRS and no neurotoxicity observed

Company to host webcast today to further review results at 11:00am ET

SAN DIEGO, Aug. 31, 2021 /PRNewswire/ -- Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage biopharmaceutical company utilizing proprietary genetic engineering platform technologies to create cell and gene therapeutics with the capacity to cure, today announced preliminary results from its Phase 1 clinical trial of P-PSMA-101, the Company's solid tumor autologous CAR-T product candidate to treat patients with metastatic castrate-resistant prostate cancer (mCRPC). These data will be presented at the 6th Annual CAR-TCR Summit virtual meeting at 10:00am ET today in a presentation entitled, "P-PSMA-101 is a High-Tscm Autologous CAR-T Targeting PSMA Producing Exceptionally Deep and Durable Responses in Castration-Resistant Metastatic Prostate Cancer."

Poseida Therapeutics (PRNewsfoto/Poseida Therapeutics, Inc.)

"We are excited about the preliminary data from our Phase 1 trial of P-PSMA-101, which provides further evidence of the effectiveness of our CAR-T platform for solid tumor cancers," said Eric Ostertag, M.D., Ph.D., Chief Executive Officer of Poseida, who will present at the CAR-TCR Summit. "To date, other CAR-T therapeutics have not had much success outside of hematologic malignancies. The deep and durable responses in our trial demonstrate that CAR-T products have the potential to work well against solid tumors, even at low doses, when using the appropriate technology platform."

Efficacy:

Story continues

As of the cutoff date, the study had enrolled a total of nine patients with mCRPC: five patients at Dose A who each received a single treatment of 0.25X10E6 cells/kg (an average of about 20M cells), and four patients at Dose B, who each received a single treatment of 0.75X10E6 cells/kg (an average of about 60M cells). All patients received a lymphodepletion regimen consisting of 30 mg/m2 fludarabine + 300 mg/m2 cyclophosphamide. Patients were heavily pre-treated, having received an average of six prior lines of therapy with a median time since diagnosis of 6.4 years.

Key findings included:

- Five patients dosed showed measurable declines in PSA levels- Three patients treated showed a greater than 50% decline in PSA levels and had concordant improvements in PSMA-PET imaging- One patient demonstrated evidence of complete tumor elimination and remains in a durable response of greater than five months at the time of this presentation

"This innovative Poseida PSMA-directed CAR T cell platform has demonstrated a robust anti-tumor response in patients with metastatic castration resistant prostate cancer," commented Susan F. Slovin, M.D., Ph.D., Associate Vice Chair of Academic Administration at Memorial Sloan Kettering Cancer Center and investigator on the trial. "This is the first time that I have seen such impressive responses with an immunotherapy product. The responses of my patients in the trial are far beyond my expectations."

Safety and Tolerability:

P-PSMA-101 demonstrated a favorable safety and tolerability profile. After a previously reported case of Macrophage Activation Syndrome (MAS) exacerbated by patient non-compliance, only three cases of possible Cytokine Release Syndrome (CRS) were observed, which were all low grade (1/2) and were managed well with early treatment. No cases of neurotoxicity (CRES/ICANS) were observed as of the cutoff date.

The Phase 1 trial is an open label, multi-center, 3+3 dose-escalating study designed to assess the safety of P-PSMA-101 in up to 40 adult subjects with mCRPC. The primary objectives of this study are to determine the safety, efficacy, and maximum tolerated dose of P-PSMA-101. Additional information about the study is available at http://www.clinicaltrials.gov using identifier: NCT04249947.

"We believe the key to success in solid tumors is a product with a high percentage of desirable stem cell memory T cells (Tscm)," said Matthew Spear, M.D., Chief Medical Officer of Poseida. "In this study, we have demonstrated that a high-percentage Tscm CAR-T product can home to the bone marrow and, in at least one case, completely eliminate tumor. This bone marrow homing property may be particularly important for bone avid diseases such as prostate adenocarcinoma. Importantly, the favorable tolerability associated with our Tscm CAR-T products has carried over to prostate cancer where we have so far seen manageable cytokine release syndrome and no neurotoxicity."

Company-Hosted Conference Call and Webcast Information

Poseida's management team will host a conference call and webcast today, August 31, 2021 at 11:00am ET. The dial-in conference call numbers for domestic and international callers are (866) 939-3921 and (678) 302-3550, respectively. The conference ID number for the call is 50220147. Participants may access the live webcast and the accompanying presentation materials on Poseida's website at http://www.poseida.com in the Investors section under Events and Presentations. An archived replay of the webcast will be available for 30 days following the event.

Additional CAR-TCR Summit Highlights

Presentation: "Developing CAR-T Cells for Multiple Myeloma: From Autologous to Allogeneic"Session Date/Time: Wednesday, September 1, 2021, 4:00pm ETPresenter: Matthew Spear, M.D., CMO, Poseida Therapeutics

This presentation will outline Phase 1 and 2 development of the Company's lead autologous P-BCMA-101 CAR-T therapy and insights that were used to develop a fully allogeneic version, P-BCMA-ALLO1 that is expected to enter the clinic soon. The presentation will be part of the afternoon session on the Clinical Management Track.

Presentation: "Advancing Nonviral Manufacturing for Multi-Product Allogeneic T-Cell Therapies"Session Date/Time: Wednesday, September 1, 2021, 4:30pm ETPresenter: Devon Shedlock, Ph.D., SVP Research & Development, Poseida Therapeutics

This presentation will discuss how Poseida's piggyBac DNA Delivery System, Cas-CLOVER Site-specific Gene Editing System and Booster Molecule are used to manufacture multi-product, fully allogeneic T-cell therapies. The Company will also discuss how efficient multiplexed Cas-CLOVER gene editing exhibits low to no off-target editing or translocations as determined by next-generation sequencing, and how the Company's Booster Molecule helps to protect against the "allo tax," maintaining a favorable high-stem cell memory T cell (Tscm) product and enabling up to hundreds of doses in a single manufacturing run. This presentation will be part of the afternoon session on the Manufacturing Track.

Presentation: "Developing 'Off-the-Shelf' CAR-T Cells for Bone Marrow Transplant Conditioning"Session Date/Time: Thursday, September 2, 2021, 9:00am ETPresenter: Nina Timberlake, Ph.D., Associate Director, Research (Gene Therapy), Poseida Therapeutics

This presentation will discuss leveraging the piggyBac DNA Delivery System and Cas-CLOVER Site-specific Gene Editing System to generate off-the-shelf fully allogeneic CAR-T cells to specifically target hematopoietic cells in the bone marrow. This potential therapeutic could be used as a non-myeloablative conditioning regimen for hematopoietic stem cell transplant or as a therapeutic for the treatment of acute myeloid leukemia (AML). The presentation will occur as part of the conference's Focus Day, "CAR-TCR Beyond Oncology: Fundamental Biology & Mechanisms of Action Beyond Oncology."

The full presentations at the CAR-TCR Summit will be made available on Poseida's website at their respective session times.

About Poseida Therapeutics, Inc.

Poseida Therapeutics is a clinical-stage biopharmaceutical company dedicated to utilizing our proprietary genetic engineering platform technologies to create next generation cell and gene therapeutics with the capacity to cure. We have discovered and are developing a broad portfolio of product candidates in a variety of indications based on our core proprietary platforms, including our non-viral piggyBac DNA Delivery System, Cas-CLOVER Site-specific Gene Editing System and nanoparticle- and AAV-based gene delivery technologies. Our core platform technologies have utility, either alone or in combination, across many cell and gene therapeutic modalities and enable us to engineer our wholly-owned portfolio of product candidates that are designed to overcome the primary limitations of current generation cell and gene therapeutics. To learn more, visit http://www.poseida.com to connect with us on Twitter and LinkedIn.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the potential benefits of Poseida's technology platforms and product candidates, Poseida's plans and strategy with respect to developing its technologies and product candidates, and anticipated timelines and milestones with respect to Poseida's development programs. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon Poseida's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with development and regulatory approval of novel product candidates in the biopharmaceutical industry and the other risks described in Poseida's filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Poseida undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

Cision

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Poseida Therapeutics Presents Preliminary Results from Phase 1 Trial of P-PSMA-101 at the 6th Annual CAR-TCR Summit - Yahoo Finance

Scientists have successfully wiped out a population of malaria-transmitting mosquitoes by using a radical form of genetic engineering to render the females infertile in the most advanced and largest ever test of use of the technology to fight the disease.

As well as bringing fresh hope in the fight against one of the worlds biggest killers, the study lays the foundations for further trials of gene-drive technology, which could mean self-destroying mosquitoes being released into the wild within 10 years.

This is a very exciting development, said Dr Thomas Price, a senior lecturer in evolution, ecology and behaviour at the University of Liverpool, who was not involved in the research. There are still lots of ethical and regulatory questions that need answering. But none of those really matter if it is impossible to build gene drives that are effective in the field. This is a major step towards achieving that.

Despite the reduction in malaria over recent decades there were still 229m cases of the disease in 2019, and 409,000 deaths.

Dr Drew Hammond, at Imperial College London, who led the new research, said: Gene drive is a self sustaining and fast acting technology that can work alongside existing tools such as bed nets, insecticides and vaccines, and could be a game changer in bringing about malaria elimination.

The development aims to bypass natural selection by plugging in a set of genetic instructions that will rapidly spread through a population and pass on a particular trait in this case infertility far faster than could be achieved through conventional selective breeding.

The idea was first mooted in 2003 but hit a roadblock when scientists discovered that their gene drives disappeared after several generations because they introduced mutations that prevented them from spreading further. Rather than giving up, Hammond and his colleagues began searching for a better target to insert their gene drive into.

Some areas of DNA are highly conserved, meaning that any mutation is likely to seriously damage their owner. Picking one of these areas could enable gene drives to survive longer.

The scientists identified a crucial sex determination gene called doublesex, which is identical across individual Anopheles gambiae mosquitoes, a species responsible for most of the malaria transmission in sub-Saharan Africa. Females mosquitoes carrying the gene drive in this gene are unable to produce offspring.

In 2018 Hammonds team used the doublesex gene drive to crash a population of about 600 A gambiae mosquitoes housed in a small cage. Within seven to 11 generations no more offspring were produced.

The same year field trials were launched in Burkina Faso by the Target Malaria research consortium, which includes the Imperial team. This involved releasing genetically modified, sterile, male mosquitoes into the wild, to test whether they could survive, and continue to be tracked an essential step towards eventual field trials of gene-drive organisms, which have not yet taken place.

The new research, published in Nature Communications, is another stepping stone towards that goal. Hammond and his colleagues tested whether the same gene drive they trialled in 2018 would spread and cause the same population collapse in closer to real-world conditions. Such testing has been flagged by the World Health Organization as a critical step before gene drive technologies can be tested in the wild.

The scientists released relatively small numbers of modified mosquitoes into much larger indoor cages housing hundreds of wild-type mosquitoes of different ages, at a research facility near Siena, central Italy. The cages were designed to entice the mosquitoes into complex mating, resting, foraging and egg-laying behaviours that would be impossible in small cages.

The researchers tracked how quickly the gene drive spread, and looked at its impact on female fertility and population decline.

This is something that has never been achieved before a single release of gene drive into a simulated field population, which brought about a crash of that entire population within a year, with no further human input. It is entirely self sustaining, said Hammond, who is also employed by the Johns Hopkins Malaria Research Institute, in Baltimore.

However, Hammond stressed that more comprehensive gene drive testing and environmental risk assessments were needed before larger field trials could take place. These could involve the release of non-sterile genetically modified mosquitoes to investigate whether they would mate with wild mosquitoes, and to what extent.

Such field trials could start within the next few years. Assuming they were successful, Hammond said he could imagine that within 10 years we would have a limited release of gene-drive mosquitoes at our field testing site, probably in Burkina Faso.

More:
Genetic engineering test with mosquitoes may be game changer in eliminating malaria - The Guardian

Cassava is a staple for one in ten people on earth, grown mostly by small farmers tending a few acres. One of the challenges is insect-vectored virus Cassava Brown-Streak Virus that destroys the root.

Scientists from Africa and the Danforth Center in St. Louis MO, USA have collaborated to create a cassava line that is genetically engineered to suppress the virus.

Follow the latest news and policy debates on agricultural biotech and biomedicine? Subscribe to our newsletter.

The approach is similar to what was done to save the papaya in Hawaii, essentially using a portion of the virus sequence to shut down viral infection.

In this weeks podcast Dr. Douglas Miano, Professor at the University of Nairobi, describes the problem and the solution. as well as how the technology may serve farmers in Kenya and the entire African continent.

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Podcast: Deploying genetic engineering to save the staple cassava vegetable in Kenya - Genetic Literacy Project

By inserting a gene found in humans and animals into potato and rice plants, an international team of scientists increased the amount of food they grew by 50% in real world tests and it also boosted photosynthesis and made them more resistant to drought.

The change really is dramatic, study co-leader Chuan He said in a press release. Whats more, it worked with almost every type of plant we tried it with so far, and its a very simple modification to make.

The challenge: About 9% of the world already doesnt have access to enough food, and climate change threatens to make the problem of food insecurity worse, causing droughts and higher temperatures that affect crop yields.

[R]eductions to agricultural productivity or sudden losses of crops or livestock will likely have ripple effects, including increased food prices and greater food insecurity, the Union of Concerned Scientists wrote in 2019.

Genetic engineering can help plants grow under hotter, drier conditions.

If we dont find ways to grow more food on less land, well have to clear more forests and plough under more and more land to feed the world.

Engineering crops: Researchers are already demonstrating ways that genetic engineering can be used to give plants characteristics that help them grow under hotter, drier conditions.

However, those approaches are often complicated, limited to one type of plant, or result in only small increases in crop yields. This new breakthrough appears to overcome all of those limitations.

Designing better rice plants: DNA contains an organisms genetic code, which is essentially an instruction manual determining what it looks like and how it functions. RNA reads those instructions and makes the proteins needed to carry them out.

But cells also place chemical tags on RNA, which affect how much protein gets made. This helps them regulate how fast they grow.

Hes team knew from previous research that a protein called FTO could erase the chemical markers on RNA potentially affecting their growth.

The study: When the scientists inserted a version of the FTO gene from animals into rice plants, the plants grew 300% more rice in the lab and 50% more under field conditions. The modified rice plants were also more resistant to drought stress, more efficient at photosynthesis, and had deeper roots.

The results were the same for potato plants.

As for how the FTO gene was able to do this, the researchers believe it affects a process called m6A, which tells plants to grow slower and stop growing sooner.

Looking ahead: The researchers are now exploring ways to trigger these same qualities in potato and rice plants without inserting another organisms gene.

It seems that plants already have this layer of regulation, and all we did is tap into it, He said. So the next step would be to discover how to do it using the plants existing genetics.

If the researchers are successful, their technique could impact more than just food insecurity.

We rely on plants for many, many things everything from wood, food, and medicine, to flowers and oil, He said, and this potentially offers a way to increase the stock material we can get from most plants.

Wed love to hear from you! If you have a comment about this article or if you have a tip for a future Freethink story, please email us at tips@freethink.com.

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Adding one gene to rice and potatoes increased yields by 50% - Freethink

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Gene therapies were once touted as a lifetime cure for crippling, costly inherited disorders. But clinical trials of the treatments are showing signs that some may lose effectiveness after five or six years. If that happens, patients could find themselves unable to receive the treatment again because they have developed antibodies to the engineered viruses that deliver most gene therapies.

Ring Therapeutics hopes it can provide gene therapies with a second act.

The privately held start-up in Cambridge, Mass., published a study Tuesday in the science journal Cell Host & Microbe about a family of viruses that Ring has engineered to deliver genetic medical treatments repeatedly because they dont provoke immune defenses. Called anelloviruses, this diverse family of viruses appears to have lived inside us, without causing disease, for as long as humans have existedsimilar to the many innocuous bacteria in our guts microbiome. Rings customized versions of these viruses could safely solve gene therapys inability to repeat dosing.

This could be a completely transformative approach to gene therapy, Ring chief executive Tuyen Ong told Barrons. Ring has protected its anellovirus technology with a moat of patent applications.

With just one peer-reviewed publication on Rings work, its still early days. The start-up has tested what it calls its Anellogy engineered-virus technology in test tubes and lab animals. It has yet to plan clinical trials in humans. If other gene therapy trials are any guides, those trials will last several years.

To bring its anellovirus technology into clinical trials, Ring said Wednesday that it has raised $117 million in a second round of funding led by its founding venture backers at Flagship Pioneering. More than an investment firm, Flagship has created and incubated dozens of biotech firms, including Covid-19 vaccine innovator Moderna (ticker: MRNA).

Ring chairman and Flagship partner Avak Kahvejian said that the growing scientific interest in the health implications of our bacterial microbiome inspired Flagship in 2017 to start searching for viruses that might also lurk harmlessly in our cells. A few anelloviruses has been discovered in the 1990s. The Flagship researchers found an unexpected variety of these viruses in different tissues of our bodies. No ones shown that these viruses cause disease. Because anelloviruses have a circle of DNA, the new venture was called Ring Therapeutics.

Most gene therapies on the marketor in clinical trialsget their therapeutic genes into a patients cells by packing a DNA cargo into hollowed-out versions of another kind of virus known as adeno-associated viruses, or AAV. Companies likeRegenxbio(RGNX) have specialized in engineering AAVs as vectors for carrying gene therapies.

But AAV vectors trigger an immune response, so they can be administered just once in a patients lifetime. If AAV gene therapy results change with time, as some clinical trials hint, they couldnt be re-administered. Because they have thrived in humans for millennia, anellovirus vectors dont seem to have that problemand Ring says that immune responses havent been seen in lab animals.

Ring CEO Ong said the company has been able to engineer anelloviruses that can carry gene therapy cargoes of similar size to the carrying capacities of AAV vectors. Ring can make vectors that target different parts of the body. And most important, its anellovirus vectors can be potentially dosed repeatedly.

Mother Nature handed us this amazing set of aces, said Ong, which have a natural advantage over other forms of viral delivery.

Corrections & amplifications: Ring Therapeutics raised $117 million in its recent private funding round. An earlier version of this article incorrectly reported the amount as $112 million.

Write to Bill Alpert at william.alpert@barrons.com

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Biotech Start-Up Ring Therapeutics Hopes to Fix a Key Shortcoming of Gene Therapies - Barron's

[Baric is referring to a 2015 collaboration with Zhengli Shi of the Wuhan Institute of Virology, or WIV, in China, which created a so-called chimera by combining the spike gene from a new bat virus with the backbone of a second virus. The spike gene determines how well a virus attaches to human cells. A detailed discussion of the research to test novel spike genes appears here.]

However, the sequence was repeatedly requested after the covid-19 pandemic emerged, and so after discussion with the NIH and the journal, it was provided to the community. Those who analyzed these sequences stated that it was very different from SARS-CoV-2.

Around 2012 or 2013, I heard Dr. Shi present at a meeting. [Shis team had recently discovered two new coronaviruses in a bat cave, which they named SHC014 and WIV1.] We talked after the meeting. I asked her whether shed be willing to make the sequences to either the SHC014 or the WIV1 spike available after she published.

And she was gracious enough to send us those sequences almost immediatelyin fact, before shed published. That was her major contribution to the paper. And when a colleague gives you sequences beforehand, coauthorship on the paper is appropriate.

That was the basis of that collaboration. We never provided the chimeric virus sequence, clones, or viruses to researchers at the WIV; and Dr. Shi, or members of her research team, never worked in our laboratory at UNC. No one from my group has worked in WIV laboratories.

Yes, but at the time, DNA synthesis costs were expensivearound a dollar per base [one letter of DNA]. So synthesizing a coronavirus genome could cost $30,000. And we only had the spike sequence. Synthesizing just the 4,000-nucleotide spike gene cost $4,000. So we introduced the authentic SHC014 spike into a replication-competent backbone: a mouse-adapted strain of SARS. The virus was viable, and we discovered that it could replicate in human cells.

So is that gain-of-function research? Well, the SARS coronavirus parental strain could replicate quite efficiently in primary human cells. The chimera could also program infection of human cells, but not better than the parental virus. So we didnt gain any functionrather, we retained function. Moreover, the chimera was attenuated in mice as compared to the parental mouse-adapted virus, so this would be considered a loss of function.

Well, by 2016, using chimeras and reverse genetics, we had identified enough high-risk SARS-like coronaviruses to be able to test and identify drugs that have broad-based activity against coronaviruses. We identified remdesivir as the first broad-based antiviral drug that worked against all known coronaviruses, and published on it in 2017. It immediately was entered into human trials and became the first FDA-approved drug for treating covid-19 infections globally. A second drug, called EIDD-2801, or molnupiravir, was also shown to be effective against all known coronaviruses prior to the 2020 pandemic, and then shown to work against SARS-CoV-2 by March 2020.

Consequently, I disagree. I would ask critics if they had identified any broad-spectrum coronavirus drugs prior to the pandemic. Can they point to papers from their laboratories documenting a strategic approach to develop effective pan-coronavirus drugs that turned out to be effective against an unknown emerging pandemic virus?

Unfortunately, remdesivir could only be delivered by intravenous injection. We were moving toward an oral-based delivery formulation, but the covid-19 pandemic emerged. I really wish wed had an oral-based drug early on. Thats the game-changer that would help people infected in the developing world, as well as citizens in the US.

Molnupiravir is an oral medication, and phase 3 trials demonstrate rapid control of viral infection. Its been considered for emergency-use authorization in India.

Finally, the work also supported federal policy decisions that prioritized basic and applied research on coronaviruses.

Around 2018 to 2019, the Vaccine Research Center at NIH contacted us to begin testing a messenger-RNA-based vaccine against MERS-CoV [a coronavirus that sometimes spreads from camels to humans]. MERS-CoV has been an ongoing problem since 2012, with a 35% mortality rate, so it has real global-health-threat potential.

By early 2020, we had a tremendous amount of data showing that in the mouse model that we had developed, these mRNA spike vaccines were really efficacious in protecting against lethal MERS-CoV infection. If designed against the original 2003 SARS strain, it was also very effective. So I think it was a no-brainer for NIH to consider mRNA-based vaccines as a safe and robust platform against SARS-CoV-2 and to give them a high priority moving forward.

Most recently, we published a paper showing that multiplexed, chimeric spike mRNA vaccines protect against all known SARS-like virus infections in mice. Global efforts to develop pan-sarbecoronavirus vaccines [sarbecoronavirus is the subgenus to which SARS and SARS-CoV-2 belong] will require us to make viruses like those described in the 2015 paper.

So I would argue that anyone saying there was no justification to do the work in 2015 is simply not acknowledging the infrastructure that contributed to therapeutics and vaccines for covid-19 and future coronaviruses.

Certainly. We do everything at BSL-3 plus. The minimum requirements at BSL-3 would be an N95 mask, eye protection, gloves, and a lab coat, but we actually wear impervious Tyvek suits, aprons, and booties and are double-gloved. Our personnel wear hoods with PAPRs [powered air-purifying respirators] that supply HEPA-filtered air to the worker. So not only are we doing all research in a biological safety cabinet, but we also perform the research in a negative-pressure containment facility, which has lots of redundant features and backups, and each worker is encased in their own private personal containment suit.

Another thing we do is to run emergency drills with local first responders. We also work with the local hospital. With many laboratory infections, theres actually no known event that caused that infection to occur. And people get sick, right? You have to have medical surveillance plans in place to rapidly quarantine people at home, to make sure they have masks and communicate regularly with a doctor on campus.

No, I dont think so. Different places have different levels of BSL-3 containment operations, standard operating procedures, and protective gear. Some of it is dependent on how deep your pockets are and the pathogens studied in the facility. An N95 is a lot cheaper than a PAPR.

Internationally, the US has no say over what biological safety conditions are used in China or any other sovereign nation to conduct research on viruses, be they coronaviruses or Nipah, Hendra, or Ebola.

Let me make it clear that we never sent any of our molecular clones or any chimeric viruses to China. They developed their own molecular clone, based on WIV1, which is a bat coronavirus. And into that backbone they shuffled in the spike genes of other bat coronaviruses, to learn how well the spike genes of these strains can promote infection in human cells.

A committee at NIH makes determinations of gain-of-function research. The gain-of-function rules are focused on viruses of pandemic potential and experiments that intend to enhance the transmissibility or pathogenesis of SARS, MERS, and avian flu strains in humans. WIV1 is approximately 10% different from SARS. Some argue that SARS coronavirus by definition covers anything in the sarbecoronavirus genus. By this definition, the Chinese might be doing gain-of-function experiments, depending on how the chimera behaves. Others argue that SARS and WIV1 are different, and as such the experiments would be exempt. Certainly, the CDC considers SARS and WIV1 to be different viruses. Only the SARS coronavirus from 2003 is a select agent. Ultimately, a committee at the NIH is the final arbiter and makes the decision about what is or is not a gain-of-function experiment.

Historically, the Chinese have done a lot of their bat coronavirus research under BSL-2 conditions. Obviously, the safety standards of BSL-2 are different than BSL-3, and lab-acquired infections occur much more frequently at BSL-2. There is also much less oversight at BSL-2.

One of the reasons I signed the letter in Science was that the WHO report didnt really discuss how work was done in the WIV laboratory, or what data the expert panel reviewed to come to the conclusion that it was very unlikely that a laboratory escape or infection was the cause of the pandemic.

There must be some recognition that a laboratory infection could have occurred under BSL-2 operating conditions. Some unknown viruses pooled from guano or oral swabs might replicate or recombine with others, so you could get new strains with unique and unpredictable biological features.

And if all this research is being performed at BSL-2, then there are questions that need to be addressed. What are the standard operating procedures in the BSL-2? What are the training records of the staff? What is the history of potential exposure events in the lab, and how were they reviewed and resolved? What are the biosafety procedures designed to prevent potential exposure events?

More:
We never created a supervirus. Ralph Baric explains gain-of-function research. - MIT Technology Review