Proof of concept studies for siRNA delivery by non-ionic surfactant vesicles : in vitro and in vivo evaluation of protein knockdown

Obeid, Mohammad A. and Dufès, Christine and Somani, Sukrut and Mullen, Alexander B. and Tate, Rothwelle J. and Ferro, Valerie A. (2018) Proof of concept studies for siRNA delivery by non-ionic surfactant vesicles : in vitro and in vivo evaluation of protein knockdown. Journal of Liposome Research. ISSN 0898-2104 (In Press)

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Abstract

RNA interference (RNAi) is an effective and naturally occurring post-transcriptional gene regulatory mechanism. This mechanism involves the degradation of a target messenger RNA (mRNA) through the introduction of short interfering RNA (siRNA) that is complementary to the target mRNA. The application of siRNA-based therapeutics is limited by the development of an effective delivery system, as naked siRNA is unstable and cannot penetrate the cell membrane. In this study, we investigated the use of cationic niosomes (CN) prepared by microfluidic mixing for siRNA delivery. In an in vitro model, these vesicles were able to deliver anti-luciferase siRNA and effectively suppress luciferase expression in B16-F10 mouse melanoma cells. More importantly, in an in vivo mouse model, intratumoral administration of CN-carrying anti-luciferase siRNA led to significant suppression of luciferase expression compared with naked siRNA. Thus, we have established a novel and effective system for the delivery of siRNA both in vitro and in vivo, which shows high potential for future application of gene therapeutics