ArticleCell2023
Human T cell generation is restored in CD3δ severe combined immunodeficiency through adenine base editing.
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Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55citing papers in PubMed
17.3field-weighted citation impact, top 1% of its field
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Who cites it
55 citing papers in PubMed, 75 citations in OpenAlex.
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- Translating base editors: a decade of progress from the bench to the clinic.Nature reviews. Drug discovery · 2026Review
- Base editing for precision therapeutics.Cell genomics · 2026Review
- Intrasplenic Thymus Organogenesis from Injectable Tissue Fragments Restores Functional T-Cell Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanistic machine learning for prediction of prime editing outcomes.Nature biotechnology · 2026Article
- ABO: A 3D stroma-supported culture platform enabling full human B-lymphopoiesis for disease modeling and gene therapy development.Cell reports. Medicine · 2026Article
- Clinical and genetic landscape of SCID in Yunnan, China: identification of two novel RAG2 variants.Scientific reports · 2026Article
- Base editing of Artemis mutations ex vivo sheds light on gene therapy for Artemis-deficient SCID.Advanced biotechnology · 2026Article
- In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder.Nature biomedical engineering · 2026Article
- Mechanistic machine learning enables interpretable and generalizable prediction of prime editing outcomes.bioRxiv : the preprint server for biology · 2026Article
- Sensitive and unbiased genome-wide profiling of base-editor-induced off-target activity using CHANGE-seq-BE.Nature biotechnology · 2026Article
- Targeting LY6E Inhibits Neuroblastoma Progression and Suppresses M2 Macrophage Polarization.Human mutation · 2026Article
- Inborn errors of immunity in Low German Mennonite communities in Mexico: a case series and narrative literature review.Frontiers in immunology · 2026Review
- Review
- CRISPR-based therapeutic genome editing for inherited blood disorders.Nature reviews. Drug discovery · 2025Review
- Recent research advances in the biological function and molecular mechanism of methylmalonic acid.Journal of Zhejiang University. Science. B · 2025Review
- Precision T cell correction platform for inborn errors of immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Gene therapy for inborn errors of immunity: past progress, current status and future directions.Rare disease and orphan drugs journal · 2025Article
- Rheumatologic and Autoimmune Features of Inborn Errors of Immunity: Implications for Diagnosis and Management.Journal of human immunity · 2025Article
- CCR5 + T cells as a potential biomarker for primary Sjögren's disease based on bioinformatics analysis.Clinical rheumatology · 2025Article
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Authors and funding
23 authors at 6 institutions in 2 countries.
Grace E McAuleyDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Gloria YiuDepartment of Medicine, Division of Rheumatology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Patrick C ChangDepartment of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Gregory A NewbyMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
Beatriz Campo-FernandezDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Sorel T Fitz-GibbonDepartment of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Xiaomeng WuDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Sung-Hae L KangDepartment of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Amber GaribayDepartment of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jeffrey ButlerDepartment of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Valentina ChristianDepartment of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Ryan L WongDepartment of Molecular & Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Kelcee A EveretteMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
Anthony AzzunDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Hila GelferDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Christopher S SeetDepartment of Medicine, Division of Hematology-Oncology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Aru NarendranDepartment of Pediatrics, University of Calgary, Calgary, AB T2N 1N4, Canada.
Luis Murguia-FavelaDepartment of Pediatrics, University of Calgary, Calgary, AB T2N 1N4, Canada.
Zulema RomeroDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Nicola WrightDepartment of Pediatrics, University of Calgary, Calgary, AB T2N 1N4, Canada.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
Gay M CrooksDepartment of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Division of Pediatric Hematology-Oncology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Donald B KohnDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular & Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Division of Pediatric Hematology-Oncology, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: dkohn1@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of Calgary · CABroad Center · USBroad Institute · USHarvard University · USHoward Hughes Medical Institute · US
Funding
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9MCenter 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
$22.7MIntegrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4MTraining in Developmental HematologyT32HL086345 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOHN, DONALD B · 2007 to 2022
$3.8MExpanding the Scope of Base EditingU01AI142756 · NIAID · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2018 to 2022
$2.1MDevelopment of a novel platform for the discovery of antigen-specific TCRsK08CA235525 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SEET, CHRISTOPHER · 2019 to 2023
$984kIn vivo precision genome editing to correct genetic diseaseR00HL163805 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI NEWBY, GREGORY A. · 2023 to 2025
$747kIn vivo precision genome editing to correct genetic diseaseK99HL163805 · NHLBI · BROAD INSTITUTE, INC. · PI NEWBY, GREGORY A. · 2022 to 2022
$167kEngineering stem cell-derived T cells for immunotherapyF31CA239555 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHANG, PATRICK C · 2020 to 2021
$73kHoward Hughes Medical InstituteNCI NIH HHS F31 CA239555NCI NIH HHS K08 CA235525NHGRI NIH HHS RM1 HG009490NHLBI NIH HHS K99 HL163805NHLBI NIH HHS R00 HL163805NHLBI NIH HHS T32 HL086345NIAID NIH HHS U01 AI142756NIGMS NIH HHS R35 GM118062NIGMS NIH HHS T32 GM008042
Abstract
CD3δ SCID is a devastating inborn error of immunity caused by mutations in CD3D, encoding the invariant CD3δ chain of the CD3/TCR complex necessary for normal thymopoiesis. We demonstrate an adenine base editing (ABE) strategy to restore CD3δ in autologous hematopoietic stem and progenitor cells (HSPCs). Delivery of mRNA encoding a laboratory-evolved ABE and guide RNA into a CD3δ SCID patient's HSPCs resulted in a 71.2% ± 7.85% (n = 3) correction of the pathogenic mutation. Edited HSPCs differentiated in artificial thymic organoids produced mature T cells exhibiting diverse TCR repertoires and TCR-dependent functions. Edited human HSPCs transplanted into immunodeficient mice showed 88% reversion of the CD3D defect in human CD34+ cells isolated from mouse bone marrow after 16 weeks, indicating correction of long-term repopulating HSCs. These findings demonstrate the preclinical efficacy of ABE in HSPCs for the treatment of CD3δ SCID, providing a foundation for the development of a one-time treatment for CD3δ SCID patients.
Indexed as
Severe Combined ImmunodeficiencyT-LymphocytesAnimalsCD3 ComplexGene EditingHumansMiceMice, SCIDReceptors, Antigen, T-CellCD3 ComplexReceptors, Antigen, T-Cellartificial thymic organoidbase editingCD3D severe combined immune deficiencyCITE-seqhematopoietic stem and progenitor cells
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