Research Spotlight: Bioreducible polymer-delivered siRNA Targeting Human Telomerase Reverse Transcriptase for Human Cancer Gene Therapy

Abstract

The success of siRNA therapeutics for cancer therapy largely depends on the delivery carrier that can safely and efficiently escort siRNA from the extracellular environment into the targeted human cancer cells. Over the past few years, disulfide-containing (bioreducible) cationic polymers have been designed, prepared and successfully applied as nonviral carriers for powerful gene/siRNA transfer, meanwhile displaying lower cytotoxicity as compared with their counterparts lacking the disulfide linkage, in part due to the intracellular degradation of the disulfide linkage. We have recently developed bioreducible disulfide-based polyethylenimine (SSPEI) for potent in vitro and in vivo delivery of siRNA targeting human telomerase reverse transcriptase (hTERT). It was found that SSPEI-delivered hTERT siRNA induced significant growth inhibition of different human cancer cells in vitro and also tumor growth suppression in vivo. Importantly, the SSPEI, at an appropriate dose, revealed a negligible adverse effect on cellular metabolic activity in vitro and liver and kidney function in vivo.

Financial & competing interests disclosure

This work was partially supported by the National Natural Science Foundation of China (No.20904041), the Innovation Program of Shanghai Municipal Education Commission (No. 10ZZ26) and the Key Scientific Project of Shanghai Putuo District (PTKW10-B01). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.