Amphiphilic Polycations for Nucleic Acid Delivery

描述(申请人提供)：鉴于其在新陈代谢、循环蛋白的分泌和感染性疾病中的核心作用，大量的遗传或获得性疾病可以通过肝脏引导的核酸输送来纠正，以灌输有益的功能或抑制有害的功能。然而，一种安全有效的将核酸分子转移到肝细胞的递送方法仍有待完善。到目前为止，大多数体内核酸输送载体都是尺寸大于50 nm的胶体颗粒。我们相信，我们已经找到了一种交付siRNA分子偶联物的创新策略。这一配方依赖于几项新的创新：作为第一阶段研究的结果-膜裂解聚合物的开发，可逆地掩蔽这些聚合物的正电荷直到它们到达酸性环境(如内小体/溶酶体)的能力，在体内将这些被掩蔽的膜裂解聚合物靶向肝细胞的能力，以及形成类似聚合物的siRNA-聚合物结合物，在体内可以靶向肝细胞。

DESCRIPTION (provided by applicant): Given its central role in metabolism, the secretion of circulating proteins, and infectious disorders, a large number of genetic or acquired disorders could be corrected by liver-directed delivery of nucleic acids to instill beneficial functions or inhibit deleterious ones. However, a safe and effective delivery method for transferring nucleic acids molecules to hepatocytes remains to be perfected. To date, most in vivo nucleic acid delivery vehicles have been colloid particles with size grater than 50 nm. We believe that we have found an innovative strategy for the delivery of molecular conjugates of siRNA. This formulation relies upon several new innovations: the development-as a result of Phase I research- of membrane lytic polymers, the ability to reversibly mask the positive charges of these polymers until they reach an acidic environment such as the endosome/lysosome, the ability to target these masked membrane lytic polymers to hepatocytes in vivo, and the formation of siRNA-polymer conjugates that like polymers can be targeted to hepatocytes in vivo.