Gene Therapy for HIV-1 Infection

Abstract

Since the discovery that AIDS is caused by a retrovirus, HIV-1, enormous efforts have been made to develop new drugs that will combat this infectious disease. Although new conventional drugs have been found to block the replication of this virus efficiently, new mutant strains continuously arise, which escape the inhibitory effect of such drugs. Furthermore, since HIV-1 integrates its genome into that of the host cell, dormant viruses persist in infected individuals over long periods. Thus, great efforts are currently being made in many laboratories to develop alternative genetic approaches to inhibit the replication of this virus. With growing insight into the mechanism and regulation of HIV-1 replication, in the past decade, many strategies have been developed and proposed for clinical application to block HIV-1 replication inside the cell. Such strategies use either antiviral RNAs or proteins (for some recent reviews, see refs. 1–4). Antiviral strategies that employ RNAs have the advantage that they are less likely to be immunogenic than protein-based antiviral agents. However, protein-based systems have been engineered using inducible promoters that only become active upon HIV-1 infection. Although such antivirals have been proved to be very effective in vitro, their beneficial effect in vivo is very difficult to evaluate and still remains to be shown. In particular, the long latent period from infection to the onset of AIDS (up to 10 years or longer) makes it very difficult to evaluate the efficacy of a new drug.