Journal Article

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

Jessica Wahlgren, Tanya De L. Karlson, Mikael Brisslert, Forugh Vaziri Sani, Esbjörn Telemo, Per Sunnerhagen and Hadi Valadi

in Nucleic Acids Research

Volume 40, issue 17, pages e130-e130
Published in print September 2012 | ISSN: 0305-1048
Published online May 2012 | e-ISSN: 1362-4962 | DOI: https://dx.doi.org/10.1093/nar/gks463

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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.

Journal Article.  6189 words.  Illustrated.

Subjects: Chemistry ; Biochemistry ; Bioinformatics and Computational Biology ; Genetics and Genomics ; Molecular and Cell Biology