Harnessing Lipid Nanoparticles as In Vivo Carriers for mRNA Encoding Monoclonal Antibodies in Inflammatory Bowel Disease

Inflammatory Bowel Disease (IBD) affects 7 million people worldwide. IBD patients require chronic treatment with heavy adverse effects that can lose efficacy over time. Consequently, many efforts are still aimed at discovering novel IBD treatments. Monoclonal antibodies (mAbs) recently emerged as a class of novel IBD therapeutics. However, mAbs pose some challenges stemming from their biological complexity, requiring intricate production, depuration, characterization, and often cause antibodies production against the generated mAb after multple injections.
mRNA encapsulation within Lipid Nanoparticles (LNPs) is an efficient strategy to express proteins in vivo. Thus, mAbs-encoding mRNA could be used to replace mAbs administration. One mRNA sequence can be translated to many mAbs molecules over days in vivo. This would lengthen mAbs half-life, lowering the administration frequency and the required dose. Furthermore, when identifying novel mAbs, their development could be sped up by their use as mRNA.
In this project, we apply Design of Experiment (DoE) to optimize LNPs to deliver mRNA ancoding for mAbs blocking integrin α₄β₇ (α₄β₇-IgG2a), a molecule involved in leukocytes migration to the inflamed gut which are responsible for IBD self-sustaining inflammation. The α₄β₇-IgG2a-encoding mRNA is produced via in vitro translation and loaded into LNPs using microfluidic mixers. The plasmatic levels of α₄β₇-IgG2a over time in vivo will be measured via ELISA assay and their therapeutic efficacy will be assessed using pathological scores in murine IBD models through colonoscopy.
This project would constitute a proof-of-concept for the development of innovative mRNA-based biological treatments and may ultimately become a novel therapeutic modality to treat IBD.