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Under the Microscope: Health Grants Highlight

IBD and Nanoparticles

This is another installment of the Rainin Foundation’s blog series, Under the Microscope: Health Grants Highlight. This series describes the terrific work of our Kenneth Rainin Foundation grantees.

In this post, we are featuring Dan Peer, PhD, of Tel Aviv University, and Eran Elinav, MD, PhD, of the Weizmann Institute of Science, and their work on nanoparticle delivery strategies to combat Inflammatory Bowel Disease (IBD). As always, we invite your thoughtful comments and feedback.

Eran Elinav and Dan Peer at the 2014 Innovations Symposium

Nanoparticles as Delivery Vehicles

Imagine an important yet fragile package delivered to your doorstep on a rainy day. Left outside, the package disintegrates; its valuable contents, ruined. This is our research challenge—to develop a delivery system for drugs that show great promise in combatting IBD, but can’t get past the body’s defenses with their disease-fighting properties intact.

For the past four years, the Kenneth Rainin Foundation has funded our efforts to develop a molecular-level delivery system that directly targets the cells responsible for IBD. This has great potential to offer effective interventions for IBD, which has proven notoriously difficult to treat, and minimize adverse side effects on patients. The Rainin Foundation’s support has allowed us to make great progress in our work, and we are grateful to them for supporting innovative research projects such as ours. Moreover, the combination of funds from the Rainin Foundation and the Helmsley Charitable Trust has helped us secure a new $2.95 million grant from the European Research Council, which will cover the next phase of our IBD research.

RNA Molecules to the Rescue

Our research has centered on ribonucleic acid interference (RNAi), in which RNA molecules disrupt the gene functions in specific cells that contribute to IBD. The allure of this potential treatment is its specificity. Small RNA molecules, either microRNAs (miRNAs) or small interfering RNAs (siRNAs), block messenger RNA (mRNA) from delivering IBD-related instructions to the body. Best, they do their blocking cell by individual cell.

Promising Development, Difficult Journey

At present, siRNAs are seen as the most promising option in RNAi therapeutics. But a crucial difficulty with siRNA delivery—and the problem that drove our Rainin-sponsored work—is its rough ride through the body. The siRNA molecules, or any drugs traveling with them, degrade rapidly in the blood. They are excreted quickly by the kidneys, and once they arrive at the proper cell, have trouble penetrating the external membrane to enter the cell. To counter this, we developed an exciting new nanoparticle delivery system, which protects this valuable package from the body’s defenses.

New Nanoparticle May Open the Door to Treatment

In our previous work, we developed the new nanoparticle, which can carry both siRNA and small drug molecules, such as the anti-inflammatory drug prednisone and the chemotherapy drug doxorubicin. In our improvements to this delivery system, we coated the surface of the nanoparticle with proteins that bind specifically to receptors on the surface of inflammatory cells associated with IBD—but not to other tissues in the body. Moreover, these proteins can be made to attach only to those inflammatory cells that are actively responding to IBD, thus avoiding the potentially disastrous side effects that would come from the nanoparticle binding to all inflammatory cells. When we tested this new delivery system on mice with Dextran Sodium Sulfate (DSS)-induced colitis, it produced an impressive therapeutic response.

On the whole, we believe that our drug delivery and treatment platform is a new systemically active and patient-tailored treatment scheme for inflammatory diseases in general and IBD in particular. Importantly, we have shown for the first time that this delivery mechanism may work in the in-vivo setting—and could eventually provide crucial treatment to IBD patients. This strategy might open new avenues for manipulating leukocyte function that could aid as a novel in-vivo drug discovery tool, as disease management, and ultimately may become a new therapeutic modality in IBD.


Drs. Peer and Elinav are scheduled to present at the following meetings:

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