Genetic-based therapies to select nonpathogenic variants of HIV-1.

Lentiviral-based genetic therapies offer a valuable addition to the current anti-HIV arsenal and allow for a rational directed approach to evolve HIV-1 to a less pathogenic state. Many lentiviral vector systems have been described that can be either replication incompetent, self-inactivating or conditionally replicating. Importantly, lentiviral vectors can be engineered to deliver anti-HIV-1 genes such as antisense RNAs, aptamers and siRNAs to those cells involved in HIV-1 infection: T-cells, hematopoietic stem cells and dendritic cells. Furthermore, the use of HIV-2-based vectors that can be mobilized by wild-type HIV-1 in vivo and spread to those cells targeted by the virus, as well as compete with HIV-1 viral RNA for packaging and access to viral proteins such as Tat and Rev required for viral replication, are of special interest. This review will focus on the rational design of therapeutic lentiviral vectors that can be used in combination with current antiretroviral therapies to essentially direct the evolution of HIV-1 to a less pathogenic state of existence.