This Small Business Innovation Research (SBIR) II project outlines in vivo testing of semi-synthetic therapeutic protein conjugates. Low molecular weight peptide drugs have had limited therapeutic utility due to rapid clearance and, consequently must be injected very frequently. These drugs could be conjugated to a carrier protein. Attachment to large biomolecules, such as carrier proteins, improves the half-life profile of these peptides. Historically, many of these carrier proteins are recombinant genetic fusions with the peptide of interest. With fusion, the carrier?s attachment to the peptide is limited to one site, the end terminus, and that limited placement can impact drug function and thus potency. As an alternative, chemical modification to carrier proteins with small molecule drugs can also render the drug more potent and longer lasting. The scientists at Redwood Bioscience have developed a technology platform that can universally modify proteins in a controlled, site-specific manner. They have generated carrier protein scaffolds, modified recombinant Fc domains that are homogeneous and easy to chemically elaborate with therapeutic peptides. Furthermore, optimized peptide conjugation to the Fc proteins improves conjugate activity in vitro. This technology is to be further validated through an initial in vivo analysis.
The broader impacts of this research are the development of best in class therapeutics and the generation of a robust protein modification platform. This work will change the utility of protein therapeutics by enabling optimization of therapeutic peptides that otherwise would not be useful as treatment for disease.
