Development of an Oral Delivery Platform for the Treatment of Inflammatory Bowel Disease

Synthetic oligonucleotides have been rising to fame in the recent two decades, and have ultimately proven their potential as therapeutic agents when they emerged as COVID-19 vaccine. One type of such agent is Antisense oligonucleotides (ASOs), that can achieve different therapeutic effects (e.g. Translation blocking, mRNA splice modulation). Despite its big promise, delivery remains the biggest challenge for the utilization of ASOs.

Lipid Nanoparticle (LNP) systems, are considered to be the most advanced, sophisticated non-viral nucleic acid delivery vehicles. We`re aiming to employ LNPs as carriers of ASOs (a combination not tested before) to examine the mucosal-membrane lack-of-integrity in Inflammatory Bowel Disease (IBD), and whether it can be used as a therapeutic advantage for the delivery of oligonucleotides into the site of inflammation. The final goal of this venture is to utilize this duo for the development of an oral delivery system for gene therapy in IBD.

In this poster, we demonstrate in-vitro toxicity and efficiency calibration of 8 LNPs formulation fabricated with novel ionizable lipids loaded with ASOs, after which 3 formulations were chosen for a preliminary in-vivo experiment to test in-vitro-in-vivo correlation. In addition to the aforementioned we demonstrated an amplification of the effectiveness of the naked ASOs by encapsulating them in LNPs, Lowering the dose tens of folds.

The purpose of these experiments was to help us establish a “Go-No Go” decision for the future in vivo experiments, in which we’ll be testing the oral delivery of few chosen formulations of the above mentioned.