Research Projects

The proposed project addresses the urgent need for scalable and accessible therapies for autoimmune diseases driven by tumor necrosis factor-alpha (TNFα), a key inflammatory mediator in several inflammatory diseases, including inflammatory bowel disease (IBD). TNFα promotes chronic inflammation by inducing pro-inflammatory cytokine production, immune cell recruitment, and tissue damage, making it an ideal therapeutic target in autoimmune disease treatment. While current monoclonal antibody therapies are effective, they are limited by high costs and complex production, restricting accessibility, particularly in low- and middle-income regions. This project proposes to use mRNA-lipid nanoparticle (LNP) technology to encode anti-TNFα antibodies, allowing in vivo production within the patient’s body, potentially reducing costs and enabling large-scale, accessible antibody therapy. The main objectives include developing mRNA constructs encoding TNFα-neutralizing antibodies based on effective FDA-approved sequences, optimizing LNP formulations for enhanced delivery, particularly to mucosal tissues relevant to IBD, and evaluating the efficacy of these mRNA-LNP antibodies in preclinical (both chemical and knockout) IBD models. Different mRNA constructs expressing anti-TNFα antibodies will be encapsulated in LNPs made from conventional lipids (such as SM-102 and ALC-0315) or mucosal-targeting lipids (L331), ensuring targeted and efficient delivery. The hypothesis is that mRNA-LNP technology can provide a potent, scalable alternative to conventional antibody therapies by efficiently producing anti-TNFα antibodies in vivo. The experimental approach will involve designing and testing mRNA constructs for expression and functionality, formulating and characterizing LNPs, and assessing the therapeutic impact of these constructs in mouse models, with a focus on immune modulation and disease outcomes. Successful completion of this project could significantly enhance our understanding of mRNA-LNP technology for antibody therapies, offering a transformative approach to managing TNFα-mediated autoimmune diseases. This research has the potential to establish a novel, cost-effective treatment strategy, substantially impacting both the fundamental understanding of mRNA-based antibody production and the practical management of chronic inflammatory conditions like IBD.