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Killing two birds with one stone: CRISPR/Cas9 CCR5 knockout hematopoietic stem cells transplantation to treat patients with HIV infection and hematological malignancies concurrently

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Abstract

Human immunodeficiency virus (HIV) is known to cause hematological malignancy. Hematopoietic stem cell transplantation (HPSCT) is an advanced treatment for that. Currently, there are three successful HIV-eliminated cases, and two received HPSCT from CCR5-absent donors. It is well established that the CCR5 protein on the cell surface assists human immunodeficiency virus entry. Preliminary studies have revealed that knocking out CCR5 and/or CXCR4 may inhibit the viral entry of HIV, which may prove promising in the further development of HIV treatment options. Herein, we suggest performing autologous or allogeneic HSCT with CCR5 KO hematopoietic stem cells in patients who suffer from complicated HIV conditions, particularly drug-resistant HIV or a concurrent diagnosis of HIV with lymphoma/leukemia, to achieve complete HIV remission. Nevertheless, at the clinical forefront of CRISPR-HIV technology, more efforts should be directed to advance nonhuman primate (NHP) models for studies of HIV pathogenesis and off-target assessments within this system.

Graphical abstract

CRISPR–Cas9 knock out of host HSCT-expressing CCR5 or CXCR4 may confer HIV-resistance, which when applied to bedside therapeutics in an allogeneic or autologous manner can warrant a permanent and effective treatment outcome.

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Acknowledgements

The graphical abstract was created with Biorender.com.

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This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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  1. Tsz Yuen Au and Jayshen Arudkumar have contributed equally to this work.

Authors and Affiliations

  1. Center for Medical Education in English, Poznan University of Medical Sciences, Poznan, Poland

    Tsz Yuen Au, Chanika Assavarittirong & Shamiram Benjamin

  2. South Australian Health and Medical Research Institute, Adelaide, SA, Australia

    Jayshen Arudkumar

  3. The University of Adelaide, Adelaide, SA, Australia

    Jayshen Arudkumar

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  1. Tsz Yuen Au
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All authors contributed to the design and implementation of the research, to the analysis of the results and to the writing of the manuscript.

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Correspondence to Jayshen Arudkumar.

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Search strategy and selection criteria

References for this review were identified through searches on PubMed and CrossRef with defined search terms such as “CRISPR HIV”, “leukemia”, “lymphoma”, “HIV” and “CCR5”. Articles were also identified through searches of the author’s own files, primarily through Google Scholar. Ongoing clinical trials were sourced from ‘ClinicalTrials.gov’. Only papers published in English were reviewed. The final reference list was generated on the basis of originality and relevance to the broad scope of this review.

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Au, T.Y., Arudkumar, J., Assavarittirong, C. et al. Killing two birds with one stone: CRISPR/Cas9 CCR5 knockout hematopoietic stem cells transplantation to treat patients with HIV infection and hematological malignancies concurrently. Clin Exp Med 23, 4163–4175 (2023). https://doi.org/10.1007/s10238-023-01129-7

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