TAU makes breakthrough in drug delivery to treat inflammatory bowel disease

To present the pioneering concept, Peer and his team encoded the anti-inflammatory protein interleukin-10 into mRNA and delivered it to animal models with Crohn's disease.

By JUDY SIEGEL-ITZKOVICH FEBRUARY 9, 2025 16:32

RESEARCHER DAN PEER: ‘We discovered that altering the proportions of lipids comprising the nanoparticles determines their destination in the bloodstream.’ (photo credit: TEL AVIV UNIVERSITY)

Developing new drugs to treat long-existing diseases is vital, but many of these medications don’t reach their targets because an organ or tissue gets in the way. 

Now, Tel Aviv University researchers have accomplished a world first, successfully delivering mRNA-based drugs to the intestine without passing through the liver. This groundbreaking development could make possible effective treatments for chronic and incurable inflammatory diseases such as Crohn’s disease and ulcerative colitis that cause much misery to their victims. 

About seven million people around the world and 15% of the US population suffer from inflammatory bowel disease (IBD), most of them developing their first signs before the age of 40, and many of them recalling the onset of symptoms during childhood or young adulthood. 

By 2019, there were 46,074 patients with IBD in Israel, corresponding to a national prevalence of 519 per 100,000, of whom 54.1% had Crohn’s and 45.9% had ulcerative colitis. 

The team members have successfully transported lipid nanoparticles encapsulating messenger RNA (mRNA) to the immune system of the small and large intestines bypassing the liver. Just changing the composition of the nanoparticles, the researchers showed that mRNA-based drugs can be directed straight to target cells, avoiding the liver. Medications meant to target specific cells in particular organs may be toxic to the liver. Drugs should not get “stuck” in the liver; ideally, the drug would reach the target organ first, and any remnants would then break down in the liver. 

A woman suffers stomach pains or cramps (Illustrative) (credit: FLICKR)

“We discovered it through random screening. We weren’t looking for it. It works this way in healthy people too,” Peer told The Jerusalem Post in an interview. 

“We are thinking about using it against colon cancer. I gave a lecture on it at a scientific conference in California, and the audience was very enthusiastic. Pharmaceutical companies that want to produce new drugs have to do clinical studies over the next year or so. It can help patients relatively fast.” 

Crohn's disease

Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract that belongs to a collection of conditions known as IBD. It is named after Dr. Burrill Crohn who first described the disease 93 years ago along with colleagues Dr. Leon Ginzburg and Dr. Gordon Oppenheimer. The disease can occur at any age but is most often diagnosed in teens and young adults. Studies have shown that between 1.5% and 28% of people with IBD have a first-degree relative such as a parent, child, or sibling who also has one of the diseases. Even though there is a genetic component associated with an increased risk of IBD, it’s impossible to predict who may get Crohn’s disease based on family history.

Crohn’s disease most commonly affects the end of the small bowel and the beginning of the colon, but inflammation of the intestine can “skip” or leave normal areas in between patches of diseased intestine. With ulcerative colitis, only the innermost lining of the colon (the large intestine) is affected, and inflammation of the intestine does not “skip.”

The research study was led by post-doctoral fellow Dr. Riccardo Rampado, together with vice president for research and development, Dan Peer, a pioneer in the development of mRNA therapeutics and director of the Laboratory of Precision Nano-Medicine at the Shmunis School of Biomedical and Cancer Research. 

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The study has just been published on the cover of the journal Advanced Science under the title “Lipid Nanoparticles With Fine-Tuned Composition Show Enhanced Colon Targeting as a Platform for mRNA Therapeutics.” 

“Everything injected into the bloodstream eventually ends up in the liver – that’s just how our anatomy works, Peer noted. “We discovered that altering the proportions of lipids comprising the nanoparticles determines their destination in the bloodstream. This is a general phenomenon, meaning it works regardless of the specific lipids, which makes this a significant breakthrough.”

To present the pioneering concept, Peer and his team encoded the anti-inflammatory protein interleukin-10 into mRNA, encapsulated it in lipid nanoparticles with a composition different from those typically used (such as in mRNA COVID-19 vaccines) and successfully delivered it to the intestines of animal models with Crohn’s disease and colitis, via intravenous injection.

“Not only were we able to deliver an mRNA-based anti-inflammatory drug directly to the inflamed intestine and improve all markers of colitis and Crohn’s disease, but we also transformed the immune cells in the intestine into factories for producing the anti-inflammatory interleukin-10,” he continued. “But this is just a proof-of-concept study. By tweaking the nanoparticle composition, we could deliver other RNA-based drugs to different organs. There’s a saying: “’’It’s all in the formulation.’ That’s exactly what this is about.”

Lipid-based drugs are encased in synthetic lipid nanoparticles that mimic biological membranes. One of these lipids is phosphatidylcholine, a component found in all biological membranes. In vaccines, such as the COVID-19 vaccine, the mRNA is encapsulated in lipid particles containing about 10% of this phospholipid. The researchers increased the ratio to 30%, causing the particles to float through the bloodstream like oil on water.

“This wasn’t a blind trial-and-error approach. We understand the mechanism, at least partially, and recognize that this ratio more closely resembles a natural biological membrane that intestinal cells are better suited to absorb,” Peer said. 

“Now, we are exploring further adjustments to target the pancreas and other organs that can be reached only by fine-tuning the lipid nanoparticle composition. 

“This direct delivery method for mRNA drugs opens up broad possibilities for developing new and more precise therapies than ever before,” he concluded.