he broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase 1 project entails developing an novel drug delivery platform to deliver drug into poorly accessible druggable targets. Drugs targeting inflammation are encapsulated in an new way for treatment of chronic inflammatory diseases such as psoriasis, lupus, rheumatoid arthritis. Biological therapies remain the standard for autoimmune diseases, but patients can have immune system problems due to the production of autoantibodies. This project addresses this challenge with a novel encapsulation technology that delivers biological therapies to hard-to-reach inflammation sites. This technology could be advantageous because it reduces immunosuppression and anti-drug antibodies production. This project will improve patient treatment outcomes and reduce treatment reduce cost.
This Small Business Innovation Research (SBIR) Phase 1 project will test a proof-of-concept that entails demonstrating that an exosome-based delivery vehicle for biologics will potentially inhibit inappropriate TLR-driven inflammation. Induction of autoimmune diseases including psoriasis, rheumatoid arthritis and lupus strongly correlate with chronic inflammation driven by inflammatory signaling pathways mediated by endosomal TLRs. Our goal is to develop an exosome-based therapy that can inhibit poorly accessible endosomal TLR7-driven inflammation. To test this concept, our plan involves genetically modifying human cell lines to produce engineered exosomes that contain anti-TLR7 antibody to inhibit endosomal TLR7-driven inflammation. We will develop a drug encapsulation platform in which engineered exosomes bear an anti-TLR7 antibody fused with an exosome transmembrane protein called tetraspanin. This complex delivers an antibody payload to TLR7 targets located in on endosomal membrane inner surface. This anti-TLR7 antibody will bind to dimer-interfaces of TLR7 monomer and thereby block TLR7 receptor dimerization, which in turn blocks proinflammatory signaling. This work is important because blocking TLR7 receptor activation, which is situated upstream in the signaling cascade, will presumably diminish immunosuppression and lead to a better outcome that current anti-TNF therapies that are more broad spectrum because their site of action is downstream in a signaling pathway axis.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
