Transcriptional Gene Silencing as a Genetic Therapy for HIV-1

The discovery of RNA interference (RNAi) has resulted in a new class of biological agents that can specifically downmodulate HIV-1 gene expression. Delivery of these RNAi-based agents and the emergence of viral resistance present pressing issues in the use of RNAi in a genetic-based therapy for HIV-1. Here, we discuss a potential avenue around viral resistance and a targeted delivery scheme for treating HIV-1-infected individuals involving transcriptional gene silencing. Specifically, the use of small antisense RNAs targeted to the viral promoter regions and delivery by lentiviral-based mobilization-competent vectors expressing these promoter targeted RNAs may prove therapeutically relevant in a genetic therapy-based approach to treating HIV-1 infection.