Delivery of RNAi-Based Oligonucleotides by Electropermeabilization.docVIP

Pharmaceuticals 2013, 6, 510-521; doi:10.3390/ph6040510 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Delivery of RNAi-Based Oligonucleotides by Electropermeabilization Sophie Chabot 1,2, Sandrine Pelofy 1,2, Justin Teissié 1,2 and Muriel Golzio 1,2, * 1 Centre National de la Recherche Scientifique (CNRS), Institut de Pharmacologie et de Biologie Structurale (IPBS) BP 64182, 205 route de Narbonne, Toulouse F-31077, France; E-Mails: sophie.chabot@ipbs.fr (S.C.); sandrine.pelofy@ipbs.fr (S.P.); justin.teissie@ipbs.fr (J.T.) Université Paul Sabatier de Toulouse, IPBS, Toulouse F-31077, France 2 * Author to whom correspondence should be addressed; E-Mail: Muriel.Golzio@ipbs.fr; Tel.: +33-561-175-811; Fax: +33-561-175-994. Received: 31 December 2012; in revised form: 19 March 2013 / Accepted: 27 March 2013 / Published: 10 April 2013 Abstract: For more than a decade, understanding of RNA interference (RNAi) has been a growing field of interest. The potent gene silencing ability that small oligonucleotides have offers new perspectives for cancer therapeutics. One of the present limits is that many biological barriers exist for their efficient delivery into target cells or tissues. Electropermeabilization (EP) is one of the physical methods successfully used to transfer small oligonucleotides into cells or tissues. EP consists in the direct application of calibrated electric pulses to cells or tissues that transiently permeabilize the plasma membranes, allowing efficient in vitro and in vivo. cytoplasmic delivery of exogenous molecules. The present review reports on the type of therapeutic RNAi-based oligonucleotides that can be electrotransferred, the mechanism(s) of their electrotransfer and the technical settings for pre-clinical purposes. Keywords: electroporation; siRNA; miRNA; LNA; siLNA 1. Introduction RNA interference (RNAi) is a natural process