siRNA Delivery Using a Smart Triblock Copolymer Carrier

描述(申请人提供)：本方案的目标是开发一种基于聚乙二醇、聚硫丙烷和小干扰RNA自组装三嵌段共聚物(PEG-PPS-S-小干扰RNA)的小干扰RNA递送系统。此外，还将合成聚乙二醇PPS-聚乙二醇-RGD聚合物，并将其用于通过整合素介导的内吞作用进行靶向内化。在体内或体外，高效地将siRNA输送到哺乳动物细胞中可以沉默基因组中的任何基因，这对研究基因功能、治疗遗传性疾病和促进组织形成具有重要意义。支持这一建议的中心假设是，三嵌段共聚物聚乙二醇-聚苯硫醚-S-小干扰RNA可以被定制，以利用细胞细胞器和细胞途径中的化学差异来实现小干扰RNA的有效传递。该系统将被开发为体内和体外预防腹壁粘连研究的核心技术，并将使许多目前不可能进行的研究成为可能。

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.