Abstract
RNA interference (RNAi) is a robust and highly evolutionarily conserved mechanism for down-regulating gene expression through targeted mRNA cleavage. It has been shown that RNAi can effectively reduce the expression of human immunodeficiency virus 1 (HIV-1) genes in vitro, but since several nucleotides of non-homology between the siRNA and the viral RNA are sufficient to significantly undermine target degradation, the emergence of resistant strains is a major potential obstacle to long term suppression of this highly mutable virus. We seek to identify quantitative design strategies for using RNAi to suppress HIV-1 in a manner that minimizes the chance of viral escape. In the results presented here, we have focused on RNAi strategies that target the viral TAR loop - a very highly conserved non-coding sequence that participates in a positive feedback loop with the viral early transcription factor, Tat.
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