Evidence map›Paper›PMID 41968583›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

Restoration of the immune system with base editing and non-genotoxic conditioning in a Rag2 point-mutant mouse model.

Carla Dib, Jack A Queenan, Hana Willner, Leah Swartzrock, Carsten T Charlesworth, Morgane Denis, Jessie R Davis, Rina J Mepani, Katie Ho, Madalena Castro and 4 more

Abstract read
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In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Carla DibDepartment of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
Jack A QueenanMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02139, USA.
Hana WillnerDepartment of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
Leah SwartzrockDepartment of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
Carsten T CharlesworthInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
Morgane DenisDepartment of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
Jessie R DavisMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02139, USA.
Rina J MepaniDepartment of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
Katie HoDepartment of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
Madalena CastroInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences at University of California, Berkeley, Berkeley, CA 94720, USA.
Ross C WilsonInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences at University of California, Berkeley, Berkeley, CA 94720, USA.
Hiromitsu NakauchiInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02139, USA.
Agnieszka CzechowiczDepartment of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: aneeshka@stanford.edu.

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
PedGeneRx - Admin Supplement to Base Editing and Prime Editing for Sickle Cell Disease R01R01HL156647 · NHLBI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Agnieszka Czechowicz, DAVID R LIU · 2021 to 2026
$4.8M
NHGRI NIH HHS RM1 HG009490NHLBI NIH HHS R01 HL156647NIGMS NIH HHS R35 GM118062
6 · The paper itself

Abstract

Transplantation of donor hematopoietic stem and progenitor cells (HSPCs) is a well-established curative treatment for various blood and immune diseases, including severe combined immunodeficiency (SCID). However, it comes with significant toxicities, including graft-versus-host disease (GvHD) and tissue damage resulting from the use of genotoxic chemotherapy-containing conditioning regimens. Autologous transplantation using gene-modified HSPCs eliminates GvHD but currently still relies on genotoxic conditioning. Further, gene modification of HSPCs has commonly utilized integrating viruses, which carry the risk of oncogenesis. The ideal therapy would eliminate the risks associated with current hematopoietic stem cell (HSC) gene-modification and conditioning approaches. Here, we combined base editors (BEs), engineered virus-like particles (eVLPs), and non-genotoxic αCD117 antibody-drug conjugate (ADC) conditioning to explore optimal curative treatment of SCID. We generated a Rag2 SCID mouse model with a single point mutation (pm) and corresponding BE. Rag2

Indexed as

DNA-Binding ProteinsGene EditingHematopoietic Stem Cell TransplantationPoint MutationSevere Combined ImmunodeficiencyTransplantation ConditioningAnimalsDisease Models, AnimalGenetic TherapyGraft vs Host DiseaseHematopoietic Stem CellsHumansImmunoconjugatesMiceMice, SCIDDNA-Binding ProteinsImmunoconjugatesRag2 protein, mousebase editingengineered virus-like particlesgene therapyhematopoietic stem cellsimmunodeficiencynon-genotoxic conditioning

Identifiers

PMID41968583
PMCPMC13330013

What OpenQuestion holds

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Registered trials

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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.