Israeli Gene Therapy Calmed Gut Disease in Mice at a 30th of the Dose

Israeli scientists have developed a gene therapy method that they say could change how inflammatory bowel diseases are treated, Tel Aviv University announced. The approach uses a class of engineered RNA molecules called locked nucleic acids, or LNAs, and produced strong anti-inflammatory effects in mice without any side effects, according to the university.

The work was published in the peer-reviewed journal Nature Communications. The team was led by Professor Dan Peer, a specialist in RNA therapeutics and nanomedicine, and included the doctoral student Shahd Qassem and the postdoctoral fellow Dr Gonna Somu Naidu. Inflammatory bowel disease, or IBD, is the umbrella term for Crohn's disease and ulcerative colitis; an estimated 6.8 million people worldwide live with it.

What locked nucleic acids are, and why they stalled

LNAs are chemically modified RNA molecules built to resist the enzymes that chew ordinary RNA apart. That stability was once seen as their great advantage. "Until about 10 years ago, they were thought to have great potential as genetic drugs," Peer said in the university's announcement. "But previous experiments showed that very high doses were needed, which caused severe side effects and made treatment costly."

The problem was never the molecule so much as the delivery: without a vehicle to steer them, the doses required to reach inflamed tissue were large enough to cause harm elsewhere in the body.

The fat-bubble carrier that shrank the dose

The team's answer was to encapsulate the LNA in a lipid nanoparticle (a microscopic bubble of fat of the kind that carried messenger RNA in COVID-19 vaccines) tuned to deliver its cargo to the inflamed gut lining. To find the right one, the researchers screened a library of lipids built up over 13 years in Peer's laboratory.

As Phys.org reported on the study, the encapsulated treatment worked at a dose 30 times lower than earlier free-LNA approaches, and improved every marker of systemic inflammation the team measured in mice with colitis. The English-language write-up published by American Friends of Tel Aviv University gives the same 30-fold figure and dates the journal publication to 18 August 2025, noting the work was carried out in collaboration with the pharmaceutical company F. Hoffmann-La Roche. "At this lower dose, delivered precisely to the correct site, the drug proved highly effective in treating the disease without causing any side effects," Peer said.

Why the target was TNF-alpha

The LNA used in the experiments silences the gene for TNF-alpha, a signalling protein that drives inflammation in IBD. That target is not a novel guess: TNF inhibitors are already a mainstay of treatment. A 2024 review in Gastroenterology Report, hosted on the US National Library of Medicine's PubMed Central, found biologic therapies including TNF inhibitors were associated with a lower risk of surgery in both Crohn's disease and ulcerative colitis. The same review put the global burden at an estimated 6.8 million IBD cases in 2017, with the highest rates in North America, Europe and Oceania.

The appeal of switching the gene off locally, rather than flooding the bloodstream with an antibody, is that the anti-inflammatory effect stays where the disease is. Peer argued the platform could stretch further: "Our study paves the way to developing new LNA-based drugs for inflammatory bowel diseases, as well as a wide range of other diseases," he said, naming rare genetic disorders, vascular and heart disease, and neurological conditions including Parkinson's and Huntington's.

What is still unclear

The results are in mice. The announcement gave no timetable for human trials, no indication of whether regulatory submissions have begun, and no estimate of what such a treatment would cost. It also did not say how long the anti-inflammatory effect lasted after dosing stopped, or how the method would be adapted for the human gut, which differs substantially from a mouse's.