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- Title
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes.
- Authors
Alvarez-Erviti, Lydia; Yiqi Seow; HaiFang Yin; Betts, Corinne; Lakhal, Samira; Wood, Matthew J. A.
- 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.
- Subjects
BIOELECTROCHEMISTRY; DENDRITIC cells; TISSUES; NEURONS; MESSENGER RNA
- Publication
Nature Biotechnology, 2011, Vol 29, Issue 4, p341
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt.1807