The use of RNA technologies to decrease HIV-1 replication and investigate the role of RNA interference in the innate immune response to HIV-1 infection

HIV-1 replication can be depressed using RNA-based methods such as antisense RNA, RNA decoys, RNA interference (RNAi) and ribozymes (Rz). Unfortunately, the virus is prone to mutation and evasion of treatment. Therefore, we propose the use of siRNA, miRNA and delta ribozymes (deltaRz) to target cellular RISC components TRBP, Ago2 and Dicer as well as viral Tat and Rev mRNAs to decrease the replication of HIV-1. Specific deltaRz that uniquely target HIV regulator genes Tat and Rev, as well as Dicer, Ago2 and TRBP have been designed. With these tools we show an efficient reduction of target proteins resulting in a decrease of HIV-1 replication up to 75%. Similarly, a reduction of the components of the RISC complex results in a near 100% decrease of HIV-1 replication. In conclusion, the RNA technologies, specifically the deltaRz have the ability to be a potent tool to reduce HIV replication and further investigate the role of RNAi in HIV-1 infection.