Efficient siRNA delivery is dependent not only on the ability of the delivery vehicle to target a specific organ but also its ability to enable siRNA entry into the cytoplasm of the target cells. Polymers with endosomolytic properties are increasingly being used as siRNA delivery vehicles due to their potential to facilitate endosomal escape and intracellular delivery. Addition of disulfide bonds in the backbone of these polymers was expected to provide degradability through reduction with glutathione in cytosol. This poster describes the synthesis of new endosomolytic bioreducible polymers that can be reversibly masked and can deliver the siRNA both in vitro and in vivo. These polymer conjugates gave good in vitro knockdown (KD) and did not demonstrate cytotoxicity in a MTS assay. Efficient mRNA KD for apolipoprotein B in mouse liver was observed with these polymer conjugates following IV dosing

Development of bioreducible polymer conjugate for siRNA delivery

244th National Meeting (2012)

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