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.
| Segura, Tatiana; Schmokel, Hugo; Hubbell, Jeffrey A (2007) RNA interference targeting hypoxia inducible factor 1alpha reduces post-operative adhesions in rats. J Surg Res 141:162-70 |
| Segura, Tatiana; Hubbell, Jeffrey A (2007) Synthesis and in vitro characterization of an ABC triblock copolymer for siRNA delivery. Bioconjug Chem 18:736-45 |
