title: Novel dual inhibitory function aptamer-siRNA delivery system for HIV-1 therapy.
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.
authors.affiliation: Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA.
authors.forename: Jiehua
authors.initials: J
authors.lastname: Zhou
authors.forename: Haitang
authors.initials: H
authors.lastname: Li
authors.forename: Shirley
authors.initials: S
authors.lastname: Li
authors.forename: John
authors.initials: J
authors.lastname: Zaia
authors.forename: John J
authors.initials: JJ
authors.lastname: Rossi
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000235:genetics*; D015152:Blotting, Northern; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005057:Eukaryotic Cells / Q000378:metabolism / Q000821:virology; D020868:Gene Silencing; D045325:HCT116 Cells; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000235:genetics / Q000628:therapy; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection / Q000379:methods
chemical_list: D052157:Aptamers, Nucleotide; D015699:HIV Envelope Protein gp120; D034741:RNA, Small Interfering