Inhibition of HIV-1 replication by siRNA targeting conserved regions of gag/pol.
Short interfering RNAs (siRNAs) targeting HIV-1gag, vif, tat, rev and host CD4 and CCR5 have been reported to inhibit HIV replication. However, the sequence divergence of HIV and the concentration dependence of siRNA activity represent significant challenges to RNAi mediated inhibition. To determine the parameters of RNAi in suppression of HIV-1 we screened seven siRNA candidates targeting highly conserved regions of gag/pol, based on target site GC content, for antiviral activity at varying concentrations. Only two of these inhibited CA-p24 production more than 50%, 2064 and 2161. Activity varied with concentration, with 100 nM producing optimal suppression. Requirements for target sequence conservation and activity over a range of concentrations may severely limit the number of siRNA candidates for therapeutic development.
Morris
Kevin V
KV
Division of Molecular Medicine, Beckman Research Institute at the City of Hope, Duarte, California 91010-3011, USA. kmorris@coh.org
Chung
Chris H
CH
Witke
Werner
W
Looney
David J
DJ
D002460:Cell Line; D017124:Conserved Sequence; D015750:Genes, gag; D015751:Genes, pol; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D014162:Transfection; D014779:Virus Replication / Q000235:genetics*
D034741:RNA, Small Interfering