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CCR5-edited gene therapies for HIV cure: Closing the door to viral entry

  • Kevin G. Haworth
    Affiliations
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
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  • Christopher W. Peterson
    Affiliations
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Department of Medicine, University of Washington, Seattle, Washington, USA
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  • Hans-Peter Kiem
    Correspondence
    Correspondence: Hans-Peter Kiem, MD, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave North Mail Stop D1-100, PO Box 19024, Seattle, WA 98109-1024, USA.
    Affiliations
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Department of Medicine, University of Washington, Seattle, Washington, USA

    Department of Pathology, University of Washington, Seattle, Washington, USA
    Search for articles by this author

      Abstract

      Human immunodeficiency virus (HIV) was first reported and characterized more than three decades ago. Once thought of as a death sentence, HIV infection has become a chronically manageable disease. However, it is estimated that a staggering 0.8% of the world's population is infected with HIV, with more than 1 million deaths reported in 2015 alone. Despite the development of effective anti-retroviral drugs, a permanent cure has only been documented in one patient to date. In 2007, an HIV-positive patient received a bone marrow transplant to treat his leukemia from an individual who was homozygous for a mutation in the CCR5 gene. This mutation, known as CCR5Δ32, prevents HIV replication by inhibiting the early stage of viral entry into cells, resulting in resistance to infection from the majority of HIV isolates. More than 10 years after his last dose of anti-retroviral therapy, the transplant recipient remains free of replication-competent virus. Multiple groups are now attempting to replicate this success through the use of other CCR5-negative donor cell sources. Additionally, developments in the use of lentiviral vectors and targeted nucleases have opened the doors of precision medicine and enabled new treatment methodologies to combat HIV infection through targeted ablation or down-regulation of CCR5 expression. Here, we review historical cases of CCR5-edited cell-based therapies, current clinical trials and future benefits and challenges associated with this technology.

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