Israel’s targeted mRNA therapy holds promise for Crohn’s disease, colitis, and beyond

The findings suggest that lipid composition can direct mRNA-based drugs to target organs, such as the intestines, without passing through the liver.

By Pesach Benson, TPS

Israeli researchers unveiled on Wednesday a new method of delivering drugs that could lead to more effective treatments for gastrointestinal conditions such as Crohn’s disease and colitis, and opens a door to targeted therapies for other conditions.

Typically, when drugs are injected into the bloodstream, they pass through the liver, where they can either be processed or broken down.

This process can limit the effectiveness of medications designed to target specific organs or cells, especially if the liver metabolizes the drugs before they can reach their intended destination.

In the case of mRNA-based drugs — which use messenger RNA (mRNA) to instruct cells to produce specific proteins that can treat or prevent disease — the liver is the primary site of drug breakdown.

However, Tel Aviv University researchers led by Dr. Riccardo Rampado and Prof. Dan Peer demonstrated that it is possible to bypass the liver and control where in the body mRNA-based drugs are delivered by altering the composition of lipid nanoparticles that encapsulate the mRNA.

The study was recently published in the peer-reviewed Advanced Science journal.

The findings suggest that lipid composition can direct mRNA-based drugs to target organs, such as the intestines, without passing through the liver.

The team’s proof-of-concept study focused on delivering mRNA encoding interleukin-10, an anti-inflammatory protein, to the intestines of animal models suffering from Crohn’s disease and colitis.

The mRNA was encapsulated in lipid nanoparticles with a higher phospholipid content than those used in typical mRNA vaccines, such as the COVID-19 vaccine.

The researchers found that increasing the phospholipid ratio to 30% enabled the particles to navigate through the bloodstream directly to the intestines.

This approach not only targeted the inflamed tissues but also encouraged immune cells in the intestine to produce the therapeutic protein, significantly improving symptoms of both conditions.

By adjusting the lipid composition, the researchers could potentially deliver mRNA-based drugs to other organs, including the pancreas, further expanding the range of treatable diseases.

“It’s all in the formulation,” Peer said.

For example, medicine might enable the targeting of immune cells in the pancreas to treat conditions like type 1 diabetes or even autoimmune disorders affecting the pancreas.

Similarly, the approach could potentially be adapted to target other organs, such as the brain, liver, or lungs, allowing for more tailored and effective therapies.

Moreover, many side effects occur as a result of drugs passing through multiple organs. Direct delivery would minimize those side effects.