title: Aptamer-targeted RNAi for HIV-1 therapy.
abstract: The highly specific mechanism of RNA (RNAi) that inhibits the expression of disease genes is increasingly being harnessed to develop a new class of therapeutics for a wide variety of human maladies. The successful use of small interfering RNAs (siRNAs) for therapeutic purposes requires safe and efficient delivery to specific cells and tissues. Herein, we demonstrate novel cell type-specific dual inhibitory function anti-gp120 aptamer-siRNA delivery systems for HIV-1 therapy, in which both the aptamer and the siRNA portions have potent anti-HIV activities. The envelope glycoprotein is expressed on the surface of HIV-1 infected cells, allowing binding and internalization of the aptamer-siRNA chimeric molecules. The Dicer substrate siRNA delivered by the aptamers is functionally processed by Dicer, resulting in specific inhibition of HIV-1 replication and infectivity in cultured CEM T-cells and primary blood mononuclear cells. Our results provide a set of novel aptamer-targeted RNAi therapeutics to combat HIV and further validate the use of anti-gp120 aptamers for delivery of Dicer substrate siRNAs.
authors: Division of Molecular and Cellular Biology, Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, City of Hope, Duarte, CA, USA.
authors: Jiehua
authors: J
authors: Zhou
authors: John J
authors: JJ
authors: Rossi
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D016466:CHO Cells; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D016503:Drug Delivery Systems; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000172:deficiency / Q000235:genetics; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D018613:Microscopy, Confocal; D058990:Molecular Targeted Therapy; D009928:Organ Specificity; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014779:Virus Replication / Q000235:genetics
chemical_list: D052157:Aptamers, Nucleotide; D016655:HIV Core Protein p24; D034741:RNA, Small Interfering