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Targeted gene disruption to cure HIV

Stone, Daniela; Kiem, Hans-Peterb,c,d; Jerome, Keith R.a,e

Current Opinion in HIV and AIDS: May 2013 - Volume 8 - Issue 3 - p 217–223
doi: 10.1097/COH.0b013e32835f736c
STATE OF HIV CURE: Edited by Françoise Barré-Sinoussi and Michael M. Lederman

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.

Summary 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.

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

Correspondence to Keith R. Jerome, MD, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, E5-110, Seattle, WA 98109, USA. Tel: +1 206 667 6793; e-mail:

© 2013 Lippincott Williams & Wilkins, Inc.