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ApexGO: AI-Driven Approach to Faster Antibiotic Discovery
ApexGO: AI-Driven Approach to Faster Antibiotic Discovery
Antibiotic resistance is on the rise around the world, creating an urgent need for faster and more dependable approaches to design antimicrobial candidates. While AI-driven methods have accelerated antimicrobial discovery, most have focused on screening fixed libraries or generating broad candidate sets.
Now, researchers at the University of Pennsylvania have developed ApexGO—a novel, AI-powered method that starts with a small number of candidates and improves them, using a predictive algorithm to evaluate each modification and guide the next.
“Antibiotic discovery is fundamentally a search problem across an enormous molecular space. ApexGO gives us a way to navigate that space with far more direction,” says César de la Fuente, PhD, presidential associate professor in the School of Engineering and Applied Science at UPenn.
This work is published Nature Machine Intelligence in the paper, “A generative artificial intelligence approach for peptide antibiotic optimization.”
“What is striking is that ApexGO’s predictions held up in the real world,” says Jacob R. Gardner, PhD, assistant professor in computer and information science (CIS) at UPenn. “ApexGO was optimizing against another computer model, so one concern was that it might find molecules that looked good to the model but failed in the lab. Instead, the majority of the molecules it designed actually worked.”
indeed, 85% of the AI-generated molecules halted bacterial growth, while 72% outperformed the peptides from which they were derived. In mice, two antimicrobial peptides created by ApexGO reduced bacterial counts at levels comparable to the antibiotic polymyxin B.
“This result points toward a future in which we can optimize molecules for a desired function in a fraction of the time,” adds de la Fuente, “using machines to guide discovery through chemical spaces too vast for humans to explore by trial and error.”
For years, the de la Fuente lab has looked for antibiotic candidates in unlikely places, from frog secretions to ancient microbes. Two years ago, the group released APEX, an AI model that predicts whether or not a given peptide is likely to have antimicrobial properties.
“APEX helped us find promising antibiotic candidates in enormous biological datasets,” says Marcelo Torres, PhD, research assistant professor of psychiatry in the Perelman School of Medicine. “ApexGO takes the next step: once we have a promising molecule, it helps us ask how to make it better.”
One part of ApexGO (short for APEX Generative Optimization) suggests molecular tweaks, while the previously published APEX model predicts whether those changes are likely to increase antimicrobial activity. ApexGO then uses those predictions to guide the next round of proposed edits.
While some of the molecules proposed by ApexGO showed promising antibiotic activity, the researchers emphasize that even the best-performing peptides are still early-stage candidates. Before any could be used to treat infections in humans, they would need to be further optimized for safety, stability, and how long they remain active in the body.
Still, the study suggests that AI can help researchers decide which molecules are worth making and testing in the first place. For de la Fuente, the approach could eventually extend beyond antibiotics. “In this case, we wanted to optimize peptides for antimicrobial activity,” he says. “But you could imagine applying the same idea to peptides with other biological functions, like modulating the immune system or targeting tumors.”
“ApexGO shows that AI can do more than predict which molecules might work: it can help us improve them,” adds de la Fuente. “At a time when antibiotic resistance is rising worldwide, we need technologies that help us move faster from an idea to a real therapeutic candidate. ApexGO is an important step toward that future.”
The post ApexGO: AI-Driven Approach to Faster Antibiotic Discovery appeared first on GEN – Genetic Engineering and Biotechnology News.
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STAT+: Trump administration revisits policy to close Medicare drug price negotiation loophole
WASHINGTON — The Trump administration on Friday proposed to change a policy that is designed to prevent drugmakers from avoiding Medicare price negotiation by adding active ingredients to drugs.
The policy is part of an annual proposed rule that establishes the process that the Centers for Medicare and Medicaid Services uses to choose the next 20 drugs and biologics for price negotiation. Those drugs will be announced by Feb. 1, 2027, and their negotiated prices will take effect in 2029. The administration also considered a similar policy last year but put off a decision to study it further.
Medicare must wait seven to 11 years after a product is approved by the Food and Drug Administration before it can negotiate its price, depending on the type of medicine. Biologics that are typically administered in doctor offices get more time than drugs taken orally.
WASHINGTON — The Trump administration on Friday proposed to change a policy that is designed to prevent drugmakers from avoiding Medicare price negotiation by adding active ingredients to drugs.
The policy is part of an annual proposed rule that establishes the process that the Centers for Medicare and Medicaid Services uses to choose the next 20 drugs and biologics for price negotiation. Those drugs will be announced by Feb. 1, 2027, and their negotiated prices will take effect in 2029. The administration also considered a similar policy last year but put off a decision to study it further.
Medicare must wait seven to 11 years after a product is approved by the Food and Drug Administration before it can negotiate its price, depending on the type of medicine. Biologics that are typically administered in doctor offices get more time than drugs taken orally.
Last month, the Andes virus outbreak on a Dutch cruise ship departing from Argentina brought a transmission context for hantavirus, that was previously unprecedented, to the forefront. The Andes virus is the only member of the hantavirus family that is capable of efficient person-to-person spread through close contact with respiratory secretions. Other hantaviruses are typically spread through contact with infected rodents, making the Andes virus a much more significant public health threat.
While at sea, the outbreak spread among passengers and crew, infecting 13 people and killing three. The cruise passengers have since returned to their home countries, 23 in total. Because a person can carry the virus for weeks before showing any symptoms, health agencies are facing a complex challenge of identifying everyone who was exposed. There are currently no vaccines or preventive treatments approved for the virus; this travel-related outbreak brought the need for vaccine development to the forefront.
Researchers at The University of Texas Medical Branch (UTMB) had previously developed and tested two mRNA vaccines against intramuscular Andes virus challenge in golden Syrian hamsters (“1-methylpseudouridine-modified or non-modified mRNA modalities encoding the envelope glycoproteins, Gn and Gc, in a single open reading frame.”)
When tested in the Syrian hamster model, both mRNA vaccines were efficacious in hamsters using a two-dose regimen. Recognizing that a fast-moving international outbreak doesn’t allow time for patients to wait weeks between shots, the team retested the vaccines to determine whether a single dose would be effective.
Now, a new report shares the finding that the vaccine provided full protection against the Andes hantavirus after a single dose.
This work is published in The Lancet in the paper, “Single-dose mRNA vaccines against Andes hantavirus.”
Alexander Bukreyev, PhD, head of the Laboratory of Viral Pathogenesis and Vaccine Development at UTMB, said that the group is working to fast-track these single-dose vaccines into human clinical trials.
The results exceeded expectations. When testing the vaccines in an animal model that mimics human disease, the scientists found that a single shot provided 100% protection against a lethal dose of the virus. Even when the researchers significantly lowered the dosage to a fraction of the original amount, the results remained definitive.
“Every vaccinated animal remained completely healthy and showed no symptoms or weight loss,” said Michelle Meyer, PhD, senior scientist in the Bukreyev Laboratory. “When we looked at the tissues from the vaccinated animals a month after infection, the virus was entirely gone. The vaccines triggered a powerful immune response, creating protective antibodies in as little as 14 days.”
Because the Andes virus can take a relatively long time to make a human severely ill, these fast-acting vaccines could serve a dual purpose, possibly functioning as an emergency tool for people who have already been exposed.
“If given quickly to high-risk contacts during an outbreak, such as the Andes virus situation on the cruise ship, the vaccines could theoretically jump-start their immune systems fast enough to intercept the virus—stopping it from replicating and preventing them from getting sick or spreading it further,” Bukreyev said.
The post Hantavirus One-Shot mRNA Vaccine Fully Protects in Syrian Hamster Model appeared first on GEN – Genetic Engineering and Biotechnology News.
Biotechnology company SonoThera has raised $125 million in an oversubscribed Series B financing round. The financing was led by Vida Ventures, with participation from ARK Invest, CureDuchenne Ventures, Leaps by Bayer, Otsuka Pharmaceutical, SymBiosis, UCB Ventures SA, Vivo Capital, and existing investors ARCH Venture Partners, Alexandria Venture Investments, Duquesne Family Office, Illumina Ventures, Johnson & Johnson Innovation – JJDC, Medical Excellence Capital, RA Capital, and Vertex Ventures HC.
SonoThera will use the funds to advance its lead programs in Duchenne muscular dystrophy (DMD) and autosomal dominant polycystic kidney disease (ADPKD) in the clinic. The funds will also support efforts to expand its pipeline of targeted redosable genetic medicines across multiple organ systems and scale its proprietary platform technologies for safe, targeted therapy delivery.
The company’s platform combines a proprietary ultrasound-mediated delivery technology dubbed RIPPLE
, with a payload engineering platform dubbed PORE. The platforms are designed to support the development of DNA and RNA therapeutics, gene editing, and gene silencing approaches. SonoThera is using its tech to develop genetic medicines that it claims will address key limitations of conventional gene therapies including delivery challenges, payload size constraints, immune responses, safety events, and difficulties with redosing.
As Kenneth Greenberd, PhD, SonoThera’s co-founder and CEO, stated “we founded SonoThera to take a fundamentally different approach, with a platform designed to broaden the therapeutic possibilities of the field. We believe our technology has the potential to expand the range of diseases addressable by genetic medicines while enabling more precise, durable, safer, and repeatable therapies for patients.”
SonoThera has already demonstrated the targeted delivery and expression capabilities of its platform across multiple tissues, including skeletal muscle, heart, liver, kidney, adipose, and brain. It has also shown that it can deliver large payloads such as full-length dystrophin for DMD and RNA-based payloads for gene silencing applications in preclinical studies.
The company expects to initiate its first clinical trial in DMD in 2027.
Commenting on the financing, Rajul Jain, MD, managing director at Vida Ventures, said “we believe SonoThera, with its RIPPLE delivery and PORE payload engineering technologies, has the potential to unlock opportunities in diseases with significant unmet need that have been previously inaccessible to other genetic medicine approaches.”
In connection with the financing, Jain and Rakhshita Dhar, MS, vice president & head of Healthcare Venture Investments at Leaps by Bayer, have joined SonoThera’s Board of Directors.
The post SonoThera Raises $125M to Develop Ultrasound-Mediated Genetic Medicines appeared first on GEN – Genetic Engineering and Biotechnology News.
Illinois’ financial crisis could bring the state to a halt
The final 6 ‘Game of Thrones’ episodes might feel like a full season
New Season 8 Walking Dead trailer flashes forward in time
Mod turns ‘Counter-Strike’ into a ‘Tekken’ clone with fighting chickens
Meet Superman’s grandfather in new trailer for Krypton
Disney’s live-action Aladdin finally finds its stars
STAT+: Trump administration revisits policy to close Medicare drug price negotiation loophole
Hantavirus One-Shot mRNA Vaccine Fully Protects in Syrian Hamster Model
SonoThera Raises $125M to Develop Ultrasound-Mediated Genetic Medicines
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FDA imposes import alert on Indian plant after inspectors flag GMP failings
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Illinois’ financial crisis could bring the state to a halt
The final 6 ‘Game of Thrones’ episodes might feel like a full season
New Season 8 Walking Dead trailer flashes forward in time
Mod turns ‘Counter-Strike’ into a ‘Tekken’ clone with fighting chickens
Meet Superman’s grandfather in new trailer for Krypton
Disney’s live-action Aladdin finally finds its stars
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