 HIV-based antisense vectors may provide several important advantages over current HIV combination therapies. VIRxSYS Corporation VIRxSYS is developing the candidate clinical vector VRX496. VRX496 is an HIV-based lentiviral vector containing an anti-HIV antisense sequence targeted to the HIV envelope env coding sequence. First, HIV-1 vectors are likely to be less toxic than current combination drug therapies because the genetic antisense antiviral is expressed only in cells that become infected with wt-HIV. The payload is located upstream of a major splice acceptor site and is thus dependent on the expression of Tat and Rev proteins that are provided by wt-HIV. Second, the length of the antisense region is over 900 nucleotides long, making it difficult for wt-HIV to create resistant strains that are sufficiently fit to cause disease. Third, HIV vectors are predicted to be safe because no novel genetic sequences are introduced into the patient i.e., no novel functional genes are contained in the HIV-1 vector. All the sequences present in the vector are derived from highly conserved regions of wt-HIV that would almost certainly be present in any HIV-1-infected individual. The HIV sequences that are used to create VRX496 are solely derived from pNL4-3, a prototypic HIV-1 molecular clone that is derived from two North American strains of HIV-1. 