Exosomes are natural carriers of exogenous siRNA to human cells in vitro

Cell Communication and Signaling

Research

Tatyana A Shtam¹  Roman A Kovalev¹  Elena Yu Varfolomeeva¹  Michael V Filatov¹  Yury V Kil²  Evgeny M Makarov³ 

[1] Division of Molecular and Radiation Biophysics, SFBI Petersburg Nuclear Physics Institute, 188300, Gatchina, Russia;Division of Molecular and Radiation Biophysics, SFBI Petersburg Nuclear Physics Institute, 188300, Gatchina, Russia;Department of Biophysics, St. Petersburg State Polytechnical University, 195251, St. Petersburg, Russia;School of Health Sciences and Social Care, Brunel University, UB8 3PH, Uxbridge, UK;

关键词: Exosomes;    RNA interference (RNAi);    Drug delivery system;    Cancer therapy;    RAD51;   

DOI  :  10.1186/1478-811X-11-88

 received in 2013-07-24, accepted in 2013-10-29,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundExosomes are nano-sized vesicles of endocytic origin that are involved in cell-to-cell communication including shuttle RNA, mainly mRNA and microRNA. As exosomes naturally carry RNA between cells, these particles might be useful in gene cancer therapy to deliver therapeutic short interfering RNA (siRNA) to the target cells. Despite the promise of RNA interference (RNAi) for use in therapy, several technical obstacles must be overcome. Exogenous siRNA is prone to degradation, has a limited ability to cross cell membranes and may induce an immune response. Naturally occurring RNA carriers, such as exosomes, might provide an untapped source of effective delivery strategies.ResultsThis study demonstrates that exosomes can deliver siRNA to recipient cells in vitro. The different strategies were used to introduce siRNAs into human exosomes of various origins. The delivery of fluorescently labeled siRNA via exosomes to cells was confirmed using confocal microscopy and flow cytometry. Two different siRNAs against RAD51 and RAD52 were used to transfect into the exosomes for therapeutic delivery into target cells. The exosome-delivered siRNAs were effective at causing post-transcriptional gene silencing in recipient cells. Moreover, the exosome-delivered siRNA against RAD51 was functional and caused the massive reproductive cell death of recipient cancer cells.ConclusionsThe results strongly suggest that exosomes effectively delivered the siRNA into the target cells. The therapeutic potential of exosome-mediated siRNA delivery was demonstrated in vitro by the strong knockdown of RAD51, a prospective therapeutic target for cancer cells. The results give an additional evidence of the ability to use human exosomes as vectors in cancer therapy, including RNAi-based gene therapy.

【 授权许可】

Unknown   
© Shtam et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.