SBIR Phase II: Design And Production Of IgG Fc Carrier Scaffolds With Increased Payload Capacity

这个小型企业创新研究（SBIR）II项目概述了半合成治疗性蛋白质结合物的体内测试。 低分子量肽药物由于快速清除而具有有限的治疗效用，因此必须非常频繁地注射。这些药物可以与载体蛋白结合。与大的生物分子如载体蛋白的连接改善了这些肽的半衰期。 历史上，这些载体蛋白中的许多是与感兴趣的肽的重组遗传融合物。有了核聚变这个载体？与肽的连接仅限于一个位点，即末端，并且有限的位置会影响药物功能，从而影响效力。作为替代方案，用小分子药物对载体蛋白进行化学修饰也可以使药物更有效和更持久。Redwood Bioscience的科学家们开发了一种技术平台，可以以受控的、位点特异性的方式对蛋白质进行普遍修饰。他们已经产生了载体蛋白支架，修饰的重组Fc结构域是同质的，易于用治疗肽进行化学修饰。此外，优化的肽与Fc蛋白的缀合改善了体外缀合物活性。 这项技术将通过初步的体内分析得到进一步验证。这项研究的更广泛影响是开发同类最佳疗法和生成强大的蛋白质修饰平台。这项工作将改变蛋白质治疗剂的效用，使治疗肽的优化，否则将无法作为疾病的治疗。

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.