Researchers at Tel Aviv University (TAU) have developed a new approach for using locked nucleic acids (LNAs), a particularly stable type of RNA, to treat inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis.

Their findings indicated improvement in all markers of systemic inflammation with no side effects. According to the researchers, this innovative method may also be suitable for a wide range of other diseases, including rare genetic disorders, vascular and heart diseases, and neurological diseases such as Parkinson’s and Huntington’s.

The study was conducted by a group associated with Professor Dan Peer, a pioneer in the use of RNA molecules for therapy and vaccines, a world expert in nanomedicine, and a senior faculty member at TAU’s Shmunis School of Biomedicine and Cancer Research, the Department of Materials Sciences and Engineering at the Iby and Aladar Fleischman Faculty of Engineering, the Jan Koum Center for Nanoscience and Nanotechnology, and the Cancer Biology Research Center. The group was led by Neubauer doctoral student Shahd Qassem and Dr. Gonna Somu Naidu, a postdoctoral fellow who collaborated with researchers from F. Hoffman La-Roche (Roche) pharmaceutical company in Switzerland. The research was published on August 18, 2025, in Nature Communications.

“Our study focused on unique RNA molecules called LNA,” Professor Peer says. “Unlike most RNA molecules, LNA molecules are very stable and do not break down easily. Consequently, until about 10 years ago, they were thought to have great potential as genetic drugs.

“However, experiments in laboratory animals, as well as clinical trials in humans with chronic liver inflammation, showed that very large amounts of LNA are needed to achieve therapeutic efficacy. Moreover, administered by injection as a free drug, this high dosage proved very costly and caused severe side effects when spreading throughout the body. As a result, the effort to develop LNA-based drugs was abandoned.

“In our study we sought to test a new, better targeted, and more effective approach.”

The researchers used a method previously developed at Professor Peer’s lab for other RNA molecules (such as siRNA, mRNA, and circRNA), now applying it to LNA: they encapsulated the molecules in lipid nanoparticles (LNPs) that serve as targeted drug carriers, delivering their therapeutic payload directly to the relevant organ in the body. Specifically, they chose an LNA molecule known to silence the TNFα gene, which plays a significant role in inflammatory bowel diseases.

Screening a lipid library developed in Professor Peer’s lab over the past 13 years, they identified the most suitable lipid molecules and encapsulated the LNA molecules in them. The resulted LNPs were injected into mice in a model of chronic bowel diseases such as colitis.

The findings were highly encouraging: the dosage required to achieve the desired therapeutic effect was 30 times lower compared to past studies in which LNA molecules were administered as a free drug without lipid encapsulation. At the current dosage, delivered precisely to the correct site, the drug proved highly effective in treating the disease, without causing any side effects.

“Our study paves the way to developing new LNA-based drugs for inflammatory bowel diseases, as well as a wide range of other diseases, including rare genetic disorders, vascular and heart diseases, and neurological diseases such as Parkinson’s and Huntington’s,” Professor Peer says. “So far, we have demonstrated that the new method is effective in chronic bowel inflammation in mice. We hope to proceed to clinical trials in humans in the near future.”