Novel Cell type-specific aptamer-siRNA delivery system for HIV-1 therapy
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- Beckman Research Institute of the City of Hope
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This manuscript is a preprint. A published version is available at:
10.1038/mt.2008.92 (Peer Reviewed) Published in Molecular Therapy (2008) 16 8, 1481–1489.- Document Type:
- Manuscript
- Date:
- Received 08 November 2007 20:57 UTC; Posted 14 November 2007
- Subjects:
- Biotechnology, Molecular Cell Biology
- Abstract:
The successful use of small interfering RNAs (siRNAs) for therapeutic purposes requires safe and efficient delivery to specific cells and tissues. Here we demonstrate cell type-specific delivery of anti-HIV siRNAs via fusion to an anti-gp120 aptamer. The envelope glycoprotein is expressed on the surface of HIV-1 infected cells, allowing binding and interalization of the aptamer-siRNA chimeric molecules. We demonstrate that the anti-gp120 aptamer-siRNA chimera is specifically taken up by cells expressing HIV-1 gp120, and the appended siRNA is processed by Dicer, releasing an anti-tat/rev siRNA which in turn inhibits HIV replication. We show for the first time a dual functioning aptamer-siRNA chimera in which both the aptamer and the siRNA portions have potent anti-HIV activities and that gp120 expressed on the surface of HIV infected cells can be used for aptamer mediated delivery of anti-HIV siRNAs.
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- This document is licensed to the public under the Creative Commons Attribution 2.5 License
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Zhou, Jiehua, Li, Haitang, Li, Shirley, Zaia, John, and Rossi, John. Novel Cell type-specific aptamer-siRNA delivery system for HIV-1 therapy. Available from Nature Precedings <http://dx.doi.org/10.1038/npre.2007.1299.1> (2007)
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Published version:
10.1038/mt.2008.92 (Peer Reviewed) Published in Molecular Therapy (2008) 16 8, 1481–1489. -
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Dan Rhoads on 19 November 2007 20:02 UTC
Interesting proof-of-concept! Wonder how it’ll fare in vivo though – will there be cross-specificity?, and can/will gp120 mutate to a non-reactive form?