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Rungta RL, Choi HB, Lin PJ, et al. Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain. Mol Ther Nucleic Acids. 2013;2:e136doi: 10.1038/mtna.2013.65.
Rungta, R. L., Choi, H. B., Lin, P. J., Ko, R. W., Ashby, D., Nair, J., Manoharan, M., Cullis, P. R., & Macvicar, B. A. (2013). Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain. Molecular therapy. Nucleic acids, 2e136. https://doi.org/10.1038/mtna.2013.65
Rungta, Ravi L, et al. "Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain." Molecular therapy. Nucleic acids vol. 2 (2013): e136. doi: https://doi.org/10.1038/mtna.2013.65
Rungta RL, Choi HB, Lin PJ, Ko RW, Ashby D, Nair J, Manoharan M, Cullis PR, Macvicar BA. Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain. Mol Ther Nucleic Acids. 2013 Dec 03;2:e136. doi: 10.1038/mtna.2013.65. PMID: 24301867; PMCID: PMC3889191.
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Mol Ther Nucleic Acids. 2013 Dec 03;2:e136. doi: 10.1038/mtna.2013.65.

Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain.

Molecular therapy. Nucleic acids

Ravi L Rungta, Hyun B Choi, Paulo Jc Lin, Rebecca Wy Ko, Donovan Ashby, Jay Nair, Muthiah Manoharan, Pieter R Cullis, Brian A Macvicar

Affiliations

  1. Brain Research Centre, Department of Psychiatry, University of British Columbia, British Columbia, Canada.

PMID: 24301867 PMCID: PMC3889191 DOI: 10.1038/mtna.2013.65

Abstract

Manipulation of gene expression in the brain is fundamental for understanding the function of proteins involved in neuronal processes. In this article, we show a method for using small interfering RNA (siRNA) in lipid nanoparticles (LNPs) to efficiently silence neuronal gene expression in cell culture and in the brain in vivo through intracranial injection. We show that neurons accumulate these LNPs in an apolipoprotein E-dependent fashion, resulting in very efficient uptake in cell culture (100%) with little apparent toxicity. In vivo, intracortical or intracerebroventricular (ICV) siRNA-LNP injections resulted in knockdown of target genes either in discrete regions around the injection site or in more widespread areas following ICV injections with no apparent toxicity or immune reactions from the LNPs. Effective targeted knockdown was demonstrated by showing that intracortical delivery of siRNA against GRIN1 (encoding GluN1 subunit of the NMDA receptor (NMDAR)) selectively reduced synaptic NMDAR currents in vivo as compared with synaptic AMPA receptor currents. Therefore, LNP delivery of siRNA rapidly manipulates expression of proteins involved in neuronal processes in vivo, possibly enabling the development of gene therapies for neurological disorders.Molecular Therapy-Nucleic Acids (2013) 2, e136; doi:10.1038/mtna.2013.65; published online 3 December 2013.

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