Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes.
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 immunog...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2011
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| _version_ | 1826265515707858944 |
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| author | Alvarez-Erviti, L Seow, Y Yin, H Betts, C Lakhal, S Wood, M |
| author_facet | Alvarez-Erviti, L Seow, Y Yin, H Betts, C Lakhal, S Wood, M |
| author_sort | Alvarez-Erviti, L |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T20:24:54Z |
| format | Journal article |
| id | oxford-uuid:2f12919d-d6fa-4817-801b-3f7350d9dc79 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:24:54Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:2f12919d-d6fa-4817-801b-3f7350d9dc792022-03-26T12:52:55ZDelivery of siRNA to the mouse brain by systemic injection of targeted exosomes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2f12919d-d6fa-4817-801b-3f7350d9dc79EnglishSymplectic Elements at Oxford2011Alvarez-Erviti, LSeow, YYin, HBetts, CLakhal, SWood, MTo 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. |
| spellingShingle | Alvarez-Erviti, L Seow, Y Yin, H Betts, C Lakhal, S Wood, M Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. |
| title | Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. |
| title_full | Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. |
| title_fullStr | Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. |
| title_full_unstemmed | Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. |
| title_short | Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. |
| title_sort | delivery of sirna to the mouse brain by systemic injection of targeted exosomes |
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