Bioreducible poly(amido amine)s for siRNA delivery

Abstract

Successes in RNA interference based therapies are still limited due to the lack of efficient delivery of the mediator, small interfering RNA (siRNA), to the targeted site. The key to success can be the delivery of the siRNA molecules by polymer-based carrier systems, since they can be chemically tailored for efficient siRNA encapsulation, protection and intracellular delivery. Recently, bioreducible poly(amido amine)s proved to be a promising class of polymers in the delivery of DNA. In this thesis the development of bioreducible poly(amido amine)s for the intracellular delivery of siRNA is reported. Polymer structure/function relationships on siRNA complexation/decomplexation, cellular delivery, gene silencing efficiency and cytotoxicity were extensively studied in vitro. The results of this thesis show great promise for future research on therapeutic applications with siRNA.