Evidence map›Paper›PMID 38508195›Full record

ArticleCell stem cell2024

Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques.

Byung-Chul Lee, Ashley Gin, Chuanfeng Wu, Komudi Singh, Max Grice, Ryland Mortlock, Diana Abraham, Xing Fan, Yifan Zhou, Aisha AlJanahi and 5 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
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

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
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  14. It's all about location: Targeting the right spot for Wiskott-Aldrich syndrome.Molecular therapy. Methods & clinical development · 2024
    Article
  15. Therapeutic Gene Editing for Hemoglobinopathies.Mediterranean journal of hematology and infectious diseases · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 3 countries.

Byung-Chul LeeTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA; Department of Biological Sciences, Sookmyung Women's University, Seoul, Korea; Research Institute of Women's Health, Sookmyung Women's University, Seoul, Korea. Electronic address: bclee@sookmyung.ac.kr.
Ashley GinTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Chuanfeng WuTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Komudi SinghTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Max GriceTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Ryland MortlockTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Diana AbrahamTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Xing FanTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Yifan ZhouTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Puddicombe Way, Cambridge, UK; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Aisha AlJanahiTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Uimook ChoiLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
Suk See DeRavinLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
Taehoon ShinTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA; Department of Laboratory Animal Medicine, College of Veterinary Medicine, Jeju National University, Jeju, Korea.
Sogun HongTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Cynthia E DunbarTranslational Stem Cell Biology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: dunbarc@nhlbi.nih.gov.
National Institutes of Health · USNational Institute of Allergy and Infectious Diseases · US

Funding

Optimization of gene transfer safety and efficacy focusing on the NHP modelZIAHL002339 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI DUNBAR, CYNTHIA E · 2009 to 2025
$26.8M
Understanding hematopoietic stem cell mobilization and engraftmentZIAHL006063 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI DUNBAR, CYNTHIA E · 2010 to 2025
$23.5M
Development and Clinical Application of Gene and Cell therapies for Patients with Immune DeficienciesZIAAI000645 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DE RAVIN, SUK SEE · 2009 to 2025
$10.1M
PRECLINICAL AND CLINICAL GENE TRANSFER TO HUMAN HEMATOPOIETIC STEM CELLSZ01HL002339 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI DUNBAR, CYNTHIA E · 1992 to 2008
$6.2M
Intramural NIH HHS Z01 HL002339Intramural NIH HHS ZIA HL006063
6 · The paper itself

Abstract

For precise genome editing via CRISPR/homology-directed repair (HDR), effective and safe editing of long-term engrafting hematopoietic stem cells (LT-HSCs) is required. The impact of HDR on true LT-HSC clonal dynamics in a relevant large animal model has not been studied. To track the output and clonality of HDR-edited cells and to provide a comparison to lentivirally transduced HSCs in vivo, we developed a competitive rhesus macaque (RM) autologous transplantation model, co-infusing HSCs transduced with a barcoded GFP-expressing lentiviral vector (LV) and HDR edited at the CD33 locus. CRISPR/HDR-edited cells showed a two-log decrease by 2 months following transplantation, with little improvement via p53 inhibition, in comparison to minimal loss of LV-transduced cells long term. HDR long-term clonality was oligoclonal in contrast to highly polyclonal LV-transduced HSCs. These results suggest marked clinically relevant differences in the impact of current genetic modification approaches on HSCs.

Indexed as

Hematopoietic Stem Cell TransplantationAnimalsClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsGene EditingHematopoietic Stem CellsLentivirusMacaca mulattaCRISPR-Cas editingex vivogenetic barcodinghematopoietic stem cellshomology-directed repairHSC gene therapylentiviral gene additionprecise genome editingrhesus macaque

Identifiers

PMID38508195
PMCPMC10997443
OpenAlexW4392950821

What OpenQuestion holds

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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.