Format

Send to

Choose Destination
See comment in PubMed Commons below
Gene Ther. 2013 Jul;20(7):695-702. doi: 10.1038/gt.2012.98. Epub 2013 Jan 31.

Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART.

Author information

1
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Abstract

The 'Berlin Patient', who maintains suppressed levels of HIV viremia in the absence of antiretroviral therapy, continues to be a standard bearer in HIV eradication research. However, the unique circumstances surrounding his functional cure are not applicable to most HIV(+) patients. To achieve a functional or sterilizing cure in a greater number of infected individuals worldwide, combinatorial treatments, targeting multiple stages of the viral life cycle, will be essential. Several anti-HIV gene therapy approaches have been explored recently, including disruption of the C-C chemokine receptor 5 (CCR5) and CXC chemokine receptor 4 (CXCR4) coreceptor loci in CD4(+) T cells and CD34(+) hematopoietic stem cells. However, less is known about the efficacy of these strategies in patients and more relevant HIV model systems such as non-human primates (NHPs). Combinatorial approaches, including genetic disruption of integrated provirus, functional enhancement of endogenous restriction factors and/or the use of pharmacological adjuvants, could amplify the anti-HIV effects of CCR5/CXCR4 gene disruption. Importantly, delivering gene disruption molecules to genetic sites of interest will likely require optimization on a cell type-by-cell type basis. In this review, we highlight the most promising gene therapy approaches to combat HIV infection, methods to deliver these therapies to hematopoietic cells and emphasize the need to target viral replication pre- and post-entry to mount a suitably robust defense against spreading infection.

PMID:
23364313
PMCID:
PMC3725618
DOI:
10.1038/gt.2012.98
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center