SBIR Phase II: Development Of An Orally Administered Gene Therapy For Granulocyte Colony-Stimulating Factor

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The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is an oral delivery platform that can deliver various drugs to the gastrointestinal tract. The market for novel biologics and oral formulations of currently injectable biologics is increasing rapidly, as is the market for gene therapies, necessitating a versatile oral drug delivery platform. This platform would positively impact society by reducing the need for repeated injections. This system would improve ease of administration of injectables by improving oral availability and the transport to the intestinal cells, and subsequent secretion of the protein into the bloodstream. This would also allow for local delivery of therapeutics for intestinal diseases which currently are hampered by poor mucus penetration and represent a multibillion-dollar market. Successful translation of this technology would benefit pharmaceutical companies, patients, and payers by providing an oral delivery platform for a broad range of therapeutics.This Small Business Innovation Research (SBIR) Phase II project addresses the problem of improving systemic expression of a protein from the gastrointestinal tract following oral lipid nanoparticle delivery. The role of digestive tract is to breakdown lipids and nucleic acids and it has therefore been very challenging to for gene delivery vehicles to survive and deliver cargo to the intestine. The project advances a new lipid nanoparticle system able to protect the genetic cargo to generate protein expression in intestinal cells later secreted into the bloodstream for systemic circulation. This process converts previously injected protein drugs into an easily administered oral drug. The research objectives are to screen and optimize several of the lipid components as well as the nucleic acid to improve secreted expression of a protein into the blood after oral delivery. This research will screen multiple formulations and cargos in vivo and measure serum protein levels after oral lipid nanoparticle delivery. The anticipated technical results are that the level of secreted protein will improve 10x from the initial formulation, further increasing the scope of potential therapeutic targets for the oral lipid nanoparticle.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.