siRNA Delivery Using a Smart Triblock Copolymer Carrier

描述（由申请人提供）：本提案的目标是开发一种基于聚乙二醇、聚丙烯硫化物和siRNA （PEG-PPS-S-siRNA）自组装三嵌段共聚物的小干扰RNA （siRNA）递送系统。此外，聚合物PEG-PPS-PEG-RGD将被合成并用于通过整合素介导的内吞作用靶向内化。在体内或体外将siRNA有效地输送到哺乳动物细胞中，有可能使基因组中的任何基因沉默，这对基因功能的研究、遗传性疾病的治疗和组织形成的增强具有重要意义。该提议的核心假设是，三嵌段共聚物PEG-PPS-S-siRNA可以被定制，以利用细胞器和细胞途径中的化学差异来实现siRNA的有效递送。该系统将作为体内和体外腹腔粘连预防研究的核心技术，并将使许多目前不可能的研究成为可能。

DESCRIPTION (provided by applicant): The goal of this proposal is to develop a delivery system for small interfering RNA (siRNA) based on the self-assembling triblock copolymers of poly (ethylene glycol), poly (propylene sulfide) and siRNA (PEG-PPS-S-siRNA). Additionally, the polymer PEG-PPS-PEG-RGD will be synthesized and used to target internalization via integrin-mediated endocytosis. Efficiently delivering siRNA to mammalian cells in vivo or in vitro has the potential to silence any gene in the genome, which has implications for the study of gene function, the treatment of inherited disorders and the augmentation of tissue formation. The central hypothesis underlying this proposal is that the triblock copolymer PEG-PPS-S-siRNA can be tailored to take advantage of chemical differences in the cell organelles and of cellular pathways to achieve efficient delivery of siRNA. This system will be developed to serve as a central technology for studies in abdominal adhesion prevention in vivo and in vitro, and will enable numerous studies that are not currently possible.