Targeted gene disruption to cure HIV

aVaccine and Infectious Disease Division bClinical Research Division, Fred Hutchinson Cancer Research Center cDepartment of Medicine dDepartment of Pathology eDepartment of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
Current opinion in HIV and AIDS (Impact Factor: 4.68). 03/2013; 8(3). DOI: 10.1097/COH.0b013e32835f736c
Source: PubMed


Purpose of review:
Recent clinical research suggests that an HIV-infected patient with lymphoma who was transplanted with bone marrow homozygous for a disrupted mutant CCR5 allele has no remaining HIV replication and is effectively cured of HIV. Here, we discuss the approaches of disrupting host and viral genes involved in HIV replication and pathogenesis with the aim of curing patients with HIV.

Recent findings:
Data from the 'Berlin patient' suggest that targeted gene disruption can lead to an HIV cure. This review discusses the recent advances in the field of gene disruption toward the development of an anti-HIV therapy. We will introduce the strategies to disrupt host and viral genes using precise disruptions, imprecise disruptions, or site-specific recombination. Furthermore, the production of engineered rare-cutting endonucleases (zinc finger nucleases, TAL effector nucleases, and homing endonucleases) and recombinases that can recognize specific DNA target sequences and facilitate gene disruption will be discussed.

The discovery of a gene disruption approach that would cure or efficiently confine HIV infection could have broad implications for the treatment of millions of people infected with HIV. An efficient 'one-shot' curative therapy not only would give infected patients hope of a drug-free or treatment-free future, but also could reduce the huge financial burden faced by many countries because of widespread administration of highly active antiretroviral therapy.

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    • "Due to the stem cell like properties, not only are memory CD4 T-cells the key cells to reconstituting patient anti-HIV immunity, but also a major HIV reservoir. Genetic and epigenetic approaches are being developed to eliminate HIV reservoirs, including targeted genome cleavage by zinc finger nucleases (ZFNs) (12–14), and epigenetic modulations such as histone deacetylation, histone methylation, and DNA methylation (1–11, 15, 69–71). As previously stated, the difference between genetic and epigenetic approaches on eradicating HIV infection is that the former changes the host cell genome, the blue print, but the later does not. "
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