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High frequency CCR5 editing in human hematopoietic stem progenitor cells protects xenograft mice from HIV infection

Author

Listed:
  • Daniel T. Claiborne

    (The Wistar Institute)

  • Zachary Detwiler

    (CRISPR Therapeutics)

  • Steffen S. Docken

    (University of New South Wales)

  • Todd D. Borland

    (CRISPR Therapeutics)

  • Deborah Cromer

    (University of New South Wales)

  • Amanda Simkhovich

    (MIT and Harvard)

  • Youdiil Ophinni

    (MIT and Harvard)

  • Ken Okawa

    (MIT and Harvard)

  • Timothy Bateson

    (MIT and Harvard)

  • Tao Chen

    (MIT and Harvard)

  • Wesley Hudson

    (MIT and Harvard)

  • Radiana Trifonova

    (MIT and Harvard)

  • Miles P. Davenport

    (University of New South Wales)

  • Tony W. Ho

    (CRISPR Therapeutics)

  • Christian L. Boutwell

    (MIT and Harvard)

  • Todd M. Allen

    (MIT and Harvard)

Abstract

The only cure of HIV has been achieved in a small number of people who received a hematopoietic stem cell transplant (HSCT) comprising allogeneic cells carrying a rare, naturally occurring, homozygous deletion in the CCR5 gene. The rarity of the mutation and the significant morbidity and mortality of such allogeneic transplants precludes widespread adoption of this HIV cure. Here, we show the application of CRISPR/Cas9 to achieve >90% CCR5 editing in human, mobilized hematopoietic stem progenitor cells (HSPC), resulting in a transplant that undergoes normal hematopoiesis, produces CCR5 null T cells, and renders xenograft mice refractory to HIV infection. Titration studies transplanting decreasing frequencies of CCR5 edited HSPCs demonstrate that

Suggested Citation

  • Daniel T. Claiborne & Zachary Detwiler & Steffen S. Docken & Todd D. Borland & Deborah Cromer & Amanda Simkhovich & Youdiil Ophinni & Ken Okawa & Timothy Bateson & Tao Chen & Wesley Hudson & Radiana T, 2025. "High frequency CCR5 editing in human hematopoietic stem progenitor cells protects xenograft mice from HIV infection," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-55873-3
    DOI: 10.1038/s41467-025-55873-3
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    References listed on IDEAS

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    1. Pietro Genovese & Giulia Schiroli & Giulia Escobar & Tiziano Di Tomaso & Claudia Firrito & Andrea Calabria & Davide Moi & Roberta Mazzieri & Chiara Bonini & Michael C. Holmes & Philip D. Gregory & Mir, 2014. "Targeted genome editing in human repopulating haematopoietic stem cells," Nature, Nature, vol. 510(7504), pages 235-240, June.
    2. Natalia Gomez-Ospina & Samantha G. Scharenberg & Nathalie Mostrel & Rasmus O. Bak & Sruthi Mantri & Rolen M. Quadros & Channabasavaiah B. Gurumurthy & Ciaran Lee & Gang Bao & Carlos J. Suarez & Shauka, 2019. "Human genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type I," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
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