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Open Access Highly Accessed Review

Cytoplasmic RNA viruses as potential vehicles for the delivery of therapeutic small RNAs

Jose A Usme-Ciro12, Natalia Campillo-Pedroza12, Fernando Almazán3 and Juan C Gallego-Gomez12*

Author Affiliations

1 Molecular and Translational Medicine Group, Facultad de Medicina, Universidad de Antioquia, Carrera 51D Nº 62 – 29, Piso 3, Edificio Histórico Manuel Uribe Ángel, Medellin, Colombia

2 Viral Vector Core & Gene Therapy, Neuroscience Group, Sede de Investigación Universitaria – SIU, Universidad de Antioquia, Medellin, Colombia

3 Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma, Darwin 3, Madrid 28049, Spain

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Virology Journal 2013, 10:185  doi:10.1186/1743-422X-10-185

Published: 7 June 2013

Abstract

Viral vectors have become the best option for the delivery of therapeutic genes in conventional and RNA interference-based gene therapies. The current viral vectors for the delivery of small regulatory RNAs are based on DNA viruses and retroviruses/lentiviruses. Cytoplasmic RNA viruses have been excluded as viral vectors for RNAi therapy because of the nuclear localization of the microprocessor complex and the potential degradation of the viral RNA genome during the excision of any virus-encoded pre-microRNAs. However, in the last few years, the presence of several species of small RNAs (e.g., virus-derived small interfering RNAs, virus-derived short RNAs, and unusually small RNAs) in animals and cell cultures that are infected with cytoplasmic RNA viruses has suggested the existence of a non-canonical mechanism of microRNA biogenesis. Several studies have been conducted on the tick-borne encephalitis virus and on the Sindbis virus in which microRNA precursors were artificially incorporated and demonstrated the production of mature microRNAs. The ability of these viruses to recruit Drosha to the cytoplasm during infection resulted in the efficient processing of virus-encoded microRNA without the viral genome entering the nucleus. In this review, we discuss the relevance of these findings with an emphasis on the potential use of cytoplasmic RNA viruses as vehicles for the efficient delivery of therapeutic small RNAs.

Keywords:
Cytoplasmic RNA viruses; Gene therapy; microRNAs; Non-canonical pathways; Viral vectors