Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2011-04

AUTHORS

Lydia Alvarez-Erviti, Yiqi Seow, HaiFang Yin, Corinne Betts, Samira Lakhal, Matthew J A Wood

ABSTRACT

To realize the therapeutic potential of RNA drugs, efficient, tissue-specific and nonimmunogenic delivery technologies must be developed. Here we show that exosomes-endogenous nano-vesicles that transport RNAs and proteins-can deliver short interfering (si)RNA to the brain in mice. To reduce immunogenicity, we used self-derived dendritic cells for exosome production. Targeting was achieved by engineering the dendritic cells to express Lamp2b, an exosomal membrane protein, fused to the neuron-specific RVG peptide. Purified exosomes were loaded with exogenous siRNA by electroporation. Intravenously injected RVG-targeted exosomes delivered GAPDH siRNA specifically to neurons, microglia, oligodendrocytes in the brain, resulting in a specific gene knockdown. Pre-exposure to RVG exosomes did not attenuate knockdown, and non-specific uptake in other tissues was not observed. The therapeutic potential of exosome-mediated siRNA delivery was demonstrated by the strong mRNA (60%) and protein (62%) knockdown of BACE1, a therapeutic target in Alzheimer's disease, in wild-type mice. More... »

PAGES

341

Journal

TITLE

Nature Biotechnology

ISSUE

4

VOLUME

29

Author Affiliations

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nbt.1807

DOI

http://dx.doi.org/10.1038/nbt.1807

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1036478917

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21423189


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