Journal
MOLECULAR THERAPY
Volume 16, Issue 8, Pages 1481-1489Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mt.2008.92
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Funding
- NHLBI NIH HHS [R01 HL074704-05A2, R01 HL074704] Funding Source: Medline
- NIAID NIH HHS [R37 AI029329-20, R37 AI029329, R01 AI042552, R01 AI042552-11] Funding Source: Medline
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The successful use of small interfering RNAs (siRNAs) for therapeutic purposes requires safe and efficient delivery to specific cells and tissues. In this study, we demonstrate cell type -specific delivery of anti-human immunodeficiency virus (anti-HIV) siRNAs through fusion to an antigp120 aptamer. The envelope glycoprotein is expressed on the surface of HIV-1-infected cells, allowing binding and internalization 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 that the appended siRNA is processed by Dicer; this releases 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. We also show that gp120 expressed on the surface of HIV-infected cells can be used for aptamermediated delivery of anti-HIV siRNAs.
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