Inhibition of HIV-1 with intracellular immunization with RNA decoys

One gene therapy approach to HIV infection, termed intracellular immunization, involves genetically modifying HIV-infectable cells with vectors which stably express a gene product which inhibits HIV gene expression and replication. One form of intracellular immunization is termed the RNA decoy strategy. RNA decoys exploit unique regulatory circuits operating in the course of HIV replication. Tat and rev are two key regulatory gene products which activate HIV gene expression by binding to specific regions of the nascent viral RNA, termed the trans-activation response (TAR) element and the rev response element (RRE), respectively. The RNA decoy strategy is based on expressing short RNA transcripts corresponding to TAR or RRE which will compete for the binding of tat or rev to their physiological targets on the viral RNA. This paper discusses the development and analysis of potent minimal RRE decoys, the gene transfer of RNA decoys into CD4+ T-cells and hematopoietic stem cells, the adeno-associated viral vectors expressing RNA decoys, as well as the future directions of this strategy.