Gene therapy for HIV infection: what does it need to make it work?

Abstract

The efficacy of antiviral drug therapy for HIV infection is limited by toxicity and viral resistance. Thus, alternative therapies need to be explored. Several gene therapeutic strategies for HIV infection have been developed, but in clinical testing therapeutically effective levels of the transgene product were not achieved. This review focuses on the determinants of therapeutic efficacy and discusses the potential and also the limits of current gene therapy approaches for HIV infection.

In vitro and in vivo cleavage of HIV-1 RNA by new SOFA-HDV ribozymes and their potential to inhibit viral replication

“…As an RNA virus, HIV is a target of choice because Rzs may target both the incoming RNA in newly infected cells and the RNA produced during the replicating cycle. 15,47 The design of SOFA-HDV Rzs should correspond to criteria of new compounds with improved efficacy and stability. The in vitro activity of the computer-designed SOFA-HDV-Rzs shows that new active compounds have been obtained (Figs.…”

“…12 Hammerhead and hairpin Rzs are currently in clinical trials against HIV, expressed from murine retroviral or lentiviral vectors. [13][14][15] Therefore, Rzs appear to have a great potential for further development of a gene-inactivation system aiming to control HIV propagation.…”

“…14,15,39,40 siRNAs have received much attention during the last years and their use against infectious agents is widely studied both in cell culture and in vivo using various methods. 41 These studies and numerous possible improvements are promising, but their use in patients will likely require their use in combination therapy to avoid viral escape.…”

Efficient entry inhibition of human and nonhuman primate immunodeficiency virus by cell surface-expressed gp41-derived peptides

“…Such approaches target critical steps in the virus life cycle, from blocking virus entry into cells to interfering with the regulation of viral gene expression, as well as priming the immune system. [1][2][3] Introducing genes that limit early steps in viral replication, like virus entry into CD4+ T cells, has the potential to select and expand HIV target cells that are resistant to infection. 2,4 Peptide-based fusion inhibitors derived from HIV gp41 C-terminal hydrophobic a-helix inhibit virus fusion by interacting with the N-terminal hydrophobic a-helix.…”

“…[1][2][3] Introducing genes that limit early steps in viral replication, like virus entry into CD4+ T cells, has the potential to select and expand HIV target cells that are resistant to infection. 2,4 Peptide-based fusion inhibitors derived from HIV gp41 C-terminal hydrophobic a-helix inhibit virus fusion by interacting with the N-terminal hydrophobic a-helix. Thus, they block conformational changes essential for membrane fusion of the virus with the host cell.…”