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.
Highlights
IntroductionRNA interference (RNAi) is a natural process allowing gene silencing at post-transcriptional level [1]
RNA interference (RNAi) is a natural process allowing gene silencing at post-transcriptional level [1].It offers the possibility of targeting and silencing any pathological protein in a specific way [2]
ECT is the combination of a cytotoxic drug, such as cisplatin or bleomycin, with electric pulses applied to the tumor
Summary
RNA interference (RNAi) is a natural process allowing gene silencing at post-transcriptional level [1]. Clinical success of RNAi has been hampered by its poor cellular uptake and stability To overcome these problems, progress has been made to develop new technologies to optimize the chemistry of siRNAs on the one hand, and achieve their effective delivery on the other hand [7]. Progress has been made to develop new technologies to optimize the chemistry of siRNAs on the one hand, and achieve their effective delivery on the other hand [7] Their physicochemical characteristics (i.e., large molecular weight and anionic charges) prevent passive diffusion across the plasma membrane of most cell types. Elucidation of the mechanisms involved in RNAi-based oligonucleotides electro-delivery will lead to a better optimization of future treatments and will allow the development of new approaches to EP-based therapy
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