I02 Systemic injection of exosomal sirna significantly reduced huntingtin expression in transgenic mice of huntington’s disease

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Cell-derived exosomes have been demonstrated to be efficient carriers of small RNAs into brain tissue. However, the therapeutic effect of exosome-mediated siRNA has not been tested in Huntington’s disease.


To explore the therapeutic potential of exosome-mediated siRNA delivery in BACHD and N171-82Q mice model.


We employed modified exosomes expressing the neuron-specific rabies viral glycoprotein (RVG) peptide loaded with siRNA targeting human huntingtin exon 1 (HuHtt) transcript. To determine the ability of modified exosomes selectively entering brain tissue, GFP-siRNA loaded exosome was administrated to GFP transgenic mice. HuHtt-siRNA RVG-exosomes was then intravenously injected to normal mice and BACHD and N171-82Q transgenic mice at 10 mg/kg every two days for 2 weeks. Performance of Rotarod test and Balance beam test was determine on N171-82Q mice post treatment.


RVG modified exosomes efficiently and specifically delivered siRNA into the mouse brain. siRNA-loaded RVG exosomes significantly reduced HuHtt mRNA and protein levels up to 46% and 54% respectively in transgenic animals. N171-82Q mice receiving RVG exosomes showed improvement on the performance of Rotarod test and Balance beam test.


Our results demonstrate that RVG exosomes can efficiently transfer siRNA to the central nervous system and HuHtt-siRNA RVG-exosomes significantly reduce huntingtin expression. The present study indicates a therapeutic potential of HuHtt-siRNA RVG-exosomes in Huntington’s disease.

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