Evidence map›Paper›PMID 39774003›Full record

ArticleNature communications2025

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

Daniel T Claiborne, Zachary Detwiler, Steffen S Docken, Todd D Borland, Deborah Cromer, Amanda Simkhovich, Youdiil Ophinni, Ken Okawa, Timothy Bateson, Tao Chen and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Searching for a HIV-1 Cure.Theranostics · 2026
    Review
  9. Review
  10. CRISPR/Cas9 for achieving postintervention HIV control.Current opinion in HIV and AIDS · 2025
    Review
  11. Article
  12. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Daniel T ClaiborneVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-2091-1456
Zachary DetwilerCRISPR Therapeutics, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2218-7334
Steffen S DockenKirby Institute, University of New South Wales, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-3771-5504
Todd D BorlandCRISPR Therapeutics, Boston, MA, USA.
Deborah CromerKirby Institute, University of New South Wales, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-5276-5094
Amanda SimkhovichRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Youdiil OphinniRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9443-1538
Ken OkawaRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Timothy BatesonRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Tao ChenRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Wesley HudsonRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Radiana TrifonovaRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Miles P DavenportKirby Institute, University of New South Wales, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-4751-1831
Tony W HoCRISPR Therapeutics, Boston, MA, USA.
Christian L BoutwellRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. cboutwell@mgh.harvard.edu.ORCID http://orcid.org/0009-0005-4715-6920
Todd M AllenRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.

Funding

Primate CoreU19HL156247 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KIEM, HANS-PETER · 2020 to 2024
$14.6M
Preclinical development of gene-edited human hematopoietic stem cellsU19HL129903 · NHLBI · HARVARD UNIVERSITY · PI SCADDEN, DAVID T · 2015 to 2019
$11.5M
NHLBI NIH HHS U19 HL129903NHLBI NIH HHS U19 HL156247
6 · The paper itself

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 <90% CCR5 editing confers decreasing protective benefit that becomes negligible between 54% and 26%. Our study demonstrates the feasibility of using CRISPR/Cas9/RNP to produce an HSPC transplant with high frequency CCR5 editing that is refractory to HIV replication. These results raise the potential of using CRISPR/Cas9 to produce a curative autologous HSCT and bring us closer to the development of a cure for HIV infection.

Indexed as

CRISPR-Cas SystemsGene EditingHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHIV InfectionsReceptors, CCR5AnimalsHeterograftsHIV-1HumansMiceMice, SCIDCCR5 protein, humanReceptors, CCR5

Identifiers

PMID39774003
PMCPMC11707138

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.