Transvascular delivery of small interfering RNA to the central nervous system View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-07

AUTHORS

Priti Kumar, Haoquan Wu, Jodi L. McBride, Kyeong-Eun Jung, Moon Hee Kim, Beverly L. Davidson, Sang Kyung Lee, Premlata Shankar, N. Manjunath

ABSTRACT

A major impediment in the treatment of neurological diseases is the presence of the blood-brain barrier, which precludes the entry of therapeutic molecules from blood to brain. Here we show that a short peptide derived from rabies virus glycoprotein (RVG) enables the transvascular delivery of small interfering RNA (siRNA) to the brain. This 29-amino-acid peptide specifically binds to the acetylcholine receptor expressed by neuronal cells. To enable siRNA binding, a chimaeric peptide was synthesized by adding nonamer arginine residues at the carboxy terminus of RVG. This RVG-9R peptide was able to bind and transduce siRNA to neuronal cells in vitro, resulting in efficient gene silencing. After intravenous injection into mice, RVG-9R delivered siRNA to the neuronal cells, resulting in specific gene silencing within the brain. Furthermore, intravenous treatment with RVG-9R-bound antiviral siRNA afforded robust protection against fatal viral encephalitis in mice. Repeated administration of RVG-9R-bound siRNA did not induce inflammatory cytokines or anti-peptide antibodies. Thus, RVG-9R provides a safe and noninvasive approach for the delivery of siRNA and potentially other therapeutic molecules across the blood-brain barrier. More... »

PAGES

39

Journal

TITLE

Nature

ISSUE

7149

VOLUME

448

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature05901

    DOI

    http://dx.doi.org/10.1038/nature05901

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1043277214

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17572664


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