Universal Protein Carrier Scaffold for Small Molecules and Peptide Therapeutics

描述(由申请人提供)：本申请涉及广泛的挑战领域(06)使能技术和特定的挑战主题，06-EB-102，生物医学技术和系统的开发低分子小分子和多肽往往由于不良的药代动力学和快速清除而具有有限的治疗效用。因此，已经有大量的努力集中在药物输送系统的开发上，包括使用大的生物分子作为载体蛋白。与其他给药方法相比，蛋白质载体提供了几个实质性的优势，包括相对较低的脱靶活性，从而产生更少的副作用。这些载体蛋白中的许多是与感兴趣的治疗性多肽的重组基因融合。或者，用小分子药物或多肽对载体蛋白进行化学加工也可以使多肽治疗更有效和更持久。当修饰是针对特定部位时，蛋白质化学修饰的最佳效益是实现的。然而，现有的位点特异性蛋白质修饰方法都不是简单、无毒、适用于在哺乳动物或细菌细胞中表达的蛋白质。因此，可以通过化学修饰来改进的多肽疗法还没有以这种方式进行优化。Redwood Bioscience Inc.开发了一种技术平台，允许我们以受控的、特定位置的方式对蛋白质进行化学修饰。最终的结果是一种在一个点上精致的蛋白质。我们相信这项技术可以用来产生运送多肽药物的载体蛋白支架。这种支架将是同质的，易于化学阐述，并导致具有成本效益的、持久的蛋白质结合疗法，以治疗未满足的医疗需求。如果成功，我们相信这项工作将通过快速使用小分子和多肽来改变蛋白质疗法的效用，否则这些小分子和多肽将不会用于疾病的治疗。与制药行业目前使用的游离肽药物或其他结合方法相比，我们的技术将产生更高质量的均一蛋白质产品，减少剂量频率，从而降低治疗成本，并具有更高的特定生物活性。这项研究最初将由一个由三名化学家和生物学家组成的团队进行，并由这笔赠款提供资金。成功完成本提案中的目标将产生必要的科学数据，以便接触外部私人资金来源。这将使我们能够发展公司，进一步发展我们的商业目标，并雇用更多的全职科学和支持人员。红木生物科学公司的醛标签技术可以用于制造修饰的人血清白蛋白。这些蛋白质将被连接到基于多肽的药物上，由此产生的结合物被证明是治疗糖尿病和骨质疏松症的有效、成本效益高的疗法。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic, 06-EB-102, Development of biomedical technologies and systems Low molecular weight small molecules and peptides often have limited therapeutic utility because of poor pharmacokinetic profile and rapid clearance. As a result, there has been a large effort focused on the development of drug delivery systems, including using large biomolecules as carrier proteins. Protein carriers offer several substantial advantages over other delivery methods including relatively low off-target activity, resulting in fewer side effects. Many of these carrier proteins are recombinant genetic fusions with a therapeutic peptide of interest. Alternately, chemically elaborating carrier proteins with small molecule drugs or peptides can also render the peptide therapeutic more potent and longer lasting. The optimal benefit of protein chemical modification is achieved when the modification is site-specific. However, none of the existing methods for site-specific protein modification are simple, non-toxic, and applicable to proteins expressed in either mammalian or bacterial cells. As a consequence, peptide therapeutics that could be improved by chemical modification have yet to be optimized in this manner. Redwood Bioscience Inc. has developed a technology platform that allows us to chemically modify proteins in a controlled, site-specific manner. The end result is a protein elaborated at a single point. We believe this technology can be used to generate a carrier protein scaffold for delivery of peptide drugs. This scaffold will be homogenous, easy to chemically elaborate, and result in cost-effective, long-lasting protein conjugate therapies to treat unmet medical needs. If successful, we believe this work will change the utility of protein therapeutics by enabling rapid use of small molecules and peptides that otherwise would not be useful as treatment for disease. Our technology will yield higher quality homogenous protein products, reduced dosage frequency resulting in lower treatment costs, and with higher specific biological activity compared to the free peptide drugs or other conjugation methods currently used in the pharmaceutical industry. The research is to be initially carried out by a team of three chemists and biologists, to be funded through this grant. Successful completion of the aims in this proposal will generate the required scientific data necessary to approach outside private sources of capital. This will allow us to grow the company and further develop our commercial targets and hire additional full time scientific and support staff. Redwood Bioscience's aldehyde-tag technology can be applied to create modified human serum albumin proteins. These proteins will be attached to peptide-based drugs and the resulting conjugates demonstrated to be efficacious, cost-effective therapies for diabetes and osteoporosis.