title: Engineering T Cells to Functionally Cure HIV-1 Infection.
abstract: Despite the ability of antiretroviral therapy to minimize human immunodeficiency virus type 1 (HIV-1) replication and increase the duration and quality of patients' lives, the health consequences and financial burden associated with the lifelong treatment regimen render a permanent cure highly attractive. Although T cells play an important role in controlling virus replication, they are themselves targets of HIV-mediated destruction. Direct genetic manipulation of T cells for adoptive cellular therapies could facilitate a functional cure by generating HIV-1-resistant cells, redirecting HIV-1-specific immune responses, or a combination of the two strategies. In contrast to a vaccine approach, which relies on the production and priming of HIV-1-specific lymphocytes within a patient's own body, adoptive T-cell therapy provides an opportunity to customize the therapeutic T cells prior to administration. However, at present, it is unclear how to best engineer T cells so that sustained control over HIV-1 replication can be achieved in the absence of antiretrovirals. This review focuses on T-cell gene-engineering and gene-editing strategies that have been performed in efforts to inhibit HIV-1 replication and highlights the requirements for a successful gene therapy-mediated functional cure.
authors.affiliation: Department of Microbiology and the Abramson Family Cancer Research Institute, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Leibman
authors.affiliation: Department of Microbiology and the Abramson Family Cancer Research Institute, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA. Electronic address: rileyj@exchange.upenn.edu.
authors.forename: James L
authors.initials: JL
authors.lastname: Riley
mesh_terms: D060846:Cell Engineering; D064987:Cell- and Tissue-Based Therapy; D015658:HIV Infections / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics