February 25

In a development that could revolutionize the treatment of inflammatory bowel diseases, Tel Aviv University researchers have created a new method to deliver mRNA-based drugs directly to the intestines while avoiding the liver.

The novel discovery could lead to more effective treatments for conditions like Crohn’s disease and colitis, and was featured on the cover of the journal Advanced Science.

Usually, when drugs are injected into our bloodstream, they end up in our liver. That can turn out to be problematic for a couple of reasons, explains TAU Prof. Dan Peer, who co-headed the research team.

“First, drugs intended to target specific cells in particular organs may be toxic to the liver,” he says. “Second, we don’t want drugs to get ‘stuck’ in the liver. Ideally, the drug would reach the target organ first, and any remnants would then break down in the liver.”

For these reasons, cutting the liver out of the equation would be ideal — and Peer and his team have discovered a way to do just that.

Increasing the amount of a certain fat molecule in tiny lipid nanoparticles, made the particles behave differently in the bloodstream, carrying medicine (in the form of mRNA molecules) straight to inflamed intestines in animal models with conditions like Crohn’s disease and colitis, bypassing the liver entirely.

New drug-delivery method promises revolution in IBD treatment — Research leaders Dr. Riccardo Rampado, left, and Prof. Dan Peer. Photo courtesy of Tel Aviv University

“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,” says Peer.

The implications of this research extend beyond intestinal diseases. The research team is already exploring how adjusting lipid compositions could target other organs and treat a wide range of conditions.

“Now, we are exploring further adjustments to target the pancreas and other organs that can only be reached by fine-tuning the lipid nanoparticle composition,” Peer says. “This direct delivery method for mRNA drugs opens up broad possibilities for developing new and more precise therapies than ever before.”