Abstract
Owing to their capacity to induce strong, sequence-specific, gene silencing in cells, short interfering RNAs (siRNAs) represent new potential therapeutic tools. This development requires, however, new safe and efficient in vivo siRNA delivery methods. In the present technical report, we show that electrically mediated siRNA transfer can suppress transgene expression in adult mice muscles. Using electropulsation for siRNA delivery opens the way for a targeted gene silencing on a broad range of tissues. Clinical applications of electropulsation for delivery of other classes of molecules are under trials. We reported that gene silencing was efficiently obtained in vivo in an adult mammal (mouse) with chemically synthesized siRNA after its electrical delivery. The associated gene silencing was followed on the same animal and lasted at least 11 days. Gene silencing was obtained in muscles not only on young adult mice but also on much older animals. No tissue damages were detected under our electrical conditions. Therefore, this method should provide an efficient approach for a localized delivery of siRNAs in various tissues and organs.
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Acknowledgements
We thank Dr M Wright for his helpful critical comments. This work was supported by grants from the CNRS (āImagerie du petit animalā program), the EU cliniporator project, the ARC (Association pour la recherche sur le cancer) and the AFM (Association franƧaise contre les myopathies). We declare that we have no competing financial interests.
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Golzio, M., Mazzolini, L., Moller, P. et al. Inhibition of gene expression in mice muscle by in vivo electrically mediated siRNA delivery. Gene Ther 12, 246ā251 (2005). https://doi.org/10.1038/sj.gt.3302405
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DOI: https://doi.org/10.1038/sj.gt.3302405