Transvascular delivery of small interfering RNA to the central nervous system
- Authors
- Kumar, Priti; Wu, Haoquan; McBride, Jodi L.; Jung, Kyeong-Eun; Kim, Moon Hee; Davidson, Beverly L.; Lee, Sang Kyung; Shankar, Premlata; Manjunath, N.
- Issue Date
- Jul-2007
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE, v.448, no.7149, pp.39 - 43
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE
- Volume
- 448
- Number
- 7149
- Start Page
- 39
- End Page
- 43
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/179898
- DOI
- 10.1038/nature05901
- ISSN
- 0028-0836
- 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.
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