Category: RNAi vs. HIV mRNA

Featured Paper:  "Lentiviral siRNAs targeting multiple highly conserved RNA sequences of human immunodeficiency virus type 1."

Authors:  L-J Chang, X Liu and J He

Year of Publication:  2005

Journal:  Gene Therapy. Vol. 12, 1133-1144

Online Availability:  Abstract from Nature.com

Significance

This category involves the traditional RNAi approach taken against HIV.  siRNAs introduced to a cell directly target the mRNA produced by the HIV provirus. 

         Experiments belonging to this category are targeted against cells that are already infected with HIV.  Therefore, this class of experiment would lead to a treatment instead of a vaccine. 

          Since HIV is a rapidly evolving virus, much care must be taken when designing or selecting the siRNAs to be used.  The siRNA should target highly conserved regions of the HIV genome, and base pair perfectly with the mRNA.  Several kinds of siRNA targeting multiple regions of HIV mRNA are usually introduced to the cell.  Experience has shown that a combination of siRNAs silence the HIV provirus far more effectively than just one kind of siRNA.

          The featured paper tested various siRNAs against two HIV-1 strains belonging to subtype B, and another strain that is a subtype A/E recombinant.  The experiment found that siRNAs targeting conserved gag, pol, int and vpu regions effectively inhibited viral replication.  However siRNAs targeting mRNAs encoding the U3, nef, or U5 regions were ineffective.  For a description of the proteins encoded by HIV, and order in which they are made (the order in which their mRNAs appear), see the HIV InSite.

A map of the HIV-1 Genome is shown to the left.