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Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes.

Journal article
Authors Jessica Wahlgren
Tanya (De L.) Karlson
Mikael Brisslert
Forugh Vazirisani
Esbjörn Telemo
Per Sunnerhagen
Hadi Valadi
Published in Nucleic acids research
Volume 40
Issue 17
Pages e130
ISSN 1362-4962
Publication year 2012
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Department of Chemistry and Molecular Biology
Pages e130
Language en
Links dx.doi.org/10.1093/nar/gks463
https://gup.ub.gu.se/file/86523
Keywords Genterapi
Subject categories Medical cell biology

Abstract

Despite the promise of RNA interference (RNAi) and its potential, e.g. for use in cancer therapy, several technical obstacles must first be overcome. The major hurdle of RNAi-based therapeutics is to deliver nucleic acids across the cell's plasma membrane. This study demonstrates that exosome vesicles derived from humans can deliver short interfering RNA (siRNA) to human mononuclear blood cells. Exosomes are nano-sized vesicles of endocytic origin that are involved in cell-to-cell communication, i.e. antigen presentation, tolerance development and shuttle RNA (mainly mRNA and microRNA). Having tested different strategies, an optimized method (electroporation) was used to introduce siRNA into human exosomes of various origins. Plasma exosomes (exosomes from peripheral blood) were used as gene delivery vector (GDV) to transport exogenous siRNA to human blood cells. The vesicles effectively delivered the administered siRNA into monocytes and lymphocytes, causing selective gene silencing of mitogen-activated protein kinase 1. These data suggest that human exosomes can be used as a GDV to provide cells with heterologous nucleic acids such as therapeutic siRNAs.

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