1. ¹Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA
2. ²Department of Virology, Beckman Research Institute of the City of Hope, Duarte, California, USA

Correspondence: John J. Rossi, Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA. E-mail: jrossi@coh.org

Received 23 February 2008; Accepted 8 April 2008; Published online 6 May 2008.

Abstract

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 anti-gp120 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 aptamer-mediated delivery of anti-HIV siRNAs.