Amphiphilic Polycations for Nucleic Acid Delivery

描述（由申请人提供）：鉴于其在代谢、循环蛋白分泌和感染性疾病中的核心作用，大量遗传或获得性疾病可以通过肝脏定向递送核酸来纠正，以灌输有益功能或抑制有害功能。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。迄今为止，大多数体内核酸传递载体都是粒径大于50纳米的胶体颗粒。我们相信我们已经找到了一种创新的siRNA分子偶联物递送策略。这种配方依赖于几个新的创新：作为第一阶段研究的结果，膜分解聚合物的开发，可逆地掩盖这些聚合物的正电荷的能力，直到它们到达酸性环境，如内核体/溶酶体，将这些被掩盖的膜分解聚合物靶向到体内肝细胞的能力，以及sirna -聚合物偶联物的形成，像聚合物一样可以靶向到体内肝细胞。

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.