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Genetic therapies against HIV

Nature Biotechnology volume 25, pages 1444–1454 (2007)Cite this article

Abstract

Highly active antiretroviral therapy prolongs the life of HIV-infected individuals, but it requires lifelong treatment and results in cumulative toxicities and viral-escape mutants. Gene therapy offers the promise of preventing progressive HIV infection by sustained interference with viral replication in the absence of chronic chemotherapy. Gene-targeting strategies are being developed with RNA-based agents, such as ribozymes, antisense, RNA aptamers and small interfering RNA, and protein-based agents, such as the mutant HIV Rev protein M10, fusion inhibitors and zinc-finger nucleases. Recent advances in T-cell–based strategies include gene-modified HIV-resistant T cells, lentiviral gene delivery, CD8+ T cells, T bodies and engineered T-cell receptors. HIV-resistant hematopoietic stem cells have the potential to protect all cell types susceptible to HIV infection. The emergence of viral resistance can be addressed by therapies that use combinations of genetic agents and that inhibit both viral and host targets. Many of these strategies are being tested in ongoing and planned clinical trials.

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Figure 1: HIV life cycle.

Katie Ris-Vicari

Figure 2

Katie Ris-Vicari

Figure 3: Adoptive immunotherapy strategies with gene-modified T cells and HS cells.

Katie Ris-Vicari

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Authors and Affiliations

  1. Division of Molecular Biology, Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, 91010, California, USA

    John J Rossi

  2. The Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Carl H June

  3. Division of Research, Departments of Pediatrics and Molecular Microbiology & Immunology, Immunology/B.M.T., Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, 90027, California, USA

    Donald B Kohn

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  1. John J Rossi
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  2. Carl H June
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  3. Donald B Kohn
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Correspondence to John J Rossi.

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Competing interests

J.J.R. is scientific advisor to Benitec, Inc., an RNAi gene therapy company, and has patents in the field of HIV gene therapy. C.H.J. receives sponsored research grant support form Sangamo Biosciences, patents and patent applications in the field of HIV gene therapy.

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Rossi, J., June, C. & Kohn, D. Genetic therapies against HIV. Nat Biotechnol 25, 1444–1454 (2007). https://doi.org/10.1038/nbt1367

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