Evidence map›Paper›PMID 36546626›Full record

Trial reportThe New England journal of medicine2022

Lentiviral Gene Therapy for Artemis-Deficient SCID.

Morton J Cowan, Jason Yu, Janelle Facchino, Carol Fraser-Browne, Ukina Sanford, Misako Kawahara, Jasmeen Dara, Janel Long-Boyle, Jess Oh, Wendy Chan and 16 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03538899 (Phase I/II Safety and Efficacy Study of Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency), which is not on this map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
5.6field-weighted citation impact, top 3% 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.

NCT03538899 phase1 / phase2recruitingnot on this map

Phase I/II Safety and Efficacy Study of Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency (ART-SCID) in Newly Diagnosed Patients Using Self-Inactivating Lentiviral Vector (AProArt) to Transduce Autologous CD34 Hematopoietic Cells

TypeinterventionalSponsorUniversity of California, San FranciscoRan2018 to 2038Enrolled24ConditionsSevere Combined ImmunodeficiencyArmsAProArt-CD34, CliniMACS® CD34 Reagent System cell sorter device, Busulfan
3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.

  1. Pooled it
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  11. Ex vivo modification of hematopoietic stem and progenitor cells for gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  12. Review
  13. Article
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  16. Article
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  18. [Advances in gene therapy for inborn errors of immunity].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 13 institutions in 3 countries.

Morton J CowanFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).ORCID 0000-0002-1088-8045
Jason YuFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Janelle FacchinoFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Carol Fraser-BrowneFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Ukina SanfordFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Misako KawaharaFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Jasmeen DaraFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Janel Long-BoyleFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Jess OhFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Wendy ChanFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Shivali ChagFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Lori BroderickFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Deepak ChellapandianFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Hélène DecaluweFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Catherine GolskiFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Diana HuFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Caroline Y KuoFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Holly K MillerFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Aleksandra PetrovicFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Robert CurrierFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Joan F HiltonFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Divya PunwaniFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Christopher C DvorakFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).ORCID 0000-0002-6146-3952
Harry L MalechFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
R Scott McIvorFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Jennifer M PuckFrom the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).ORCID 0000-0001-6623-6276
JDSU (United States) · USUCSF Benioff Children's Hospital · USCardiovascular Institute Hospital · JPTuba City Regional Health Care · USCancer Research And Biostatistics · USCentre Hospitalier Universitaire Sainte-Justine · CAJohns Hopkins University · USMattel Children's Hospital · USNational Institutes of Health · USPhoenix Children's Hospital · USSeattle Children's Hospital · USUniversity of California San Diego · USUniversity of Minnesota · US

Funding

Training of Clinical Investigators in Primary Immune DeficienciesU54AI082973 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MALECH, HARRY · 2009 to 2023
$23.3M
Inherited T cell defects: Diagnosis, Mechanisms and TreatmentsP01AI138962 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BRENNER, STEVEN E · 2020 to 2024
$11.3M
Primary Immune Deficiency Treatment Consortium Annual Scientific MeetingR13AI094943 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PUCK, JENNIFER M. · 2011 to 2025
$239k
California Institute for Regenerative Medicine CLIN2-10830National Institute of Allergy and Infectious Diseases U54-AI082973NIAID NIH HHS P01 AI138962NIAID NIH HHS R13 AI094943NIAID NIH HHS U54 AI082973
6 · The paper itself

Abstract

backgroundThe DNA-repair enzyme Artemis is essential for rearrangement of T- and B-cell receptors. Mutations in

methodsWe carried out a phase 1-2 clinical study of the transfusion of autologous CD34+ cells, transfected with a lentiviral vector containing

resultsMarrow harvest, busulfan conditioning, and lentiviral-transduced CD34+ cell infusion produced the expected grade 3 or 4 adverse events. All the procedures met prespecified criteria for feasibility at 42 days after infusion. Gene-marked T cells were detected at 6 to 16 weeks after infusion in all the patients. Five of 6 patients who were followed for at least 24 months had T-cell immune reconstitution at a median of 12 months. The diversity of T-cell receptor β chains normalized by 6 to 12 months. Four patients who were followed for at least 24 months had sufficient B-cell numbers, IgM concentration, or IgM isohemagglutinin titers to permit discontinuation of IgG infusions. Three of these 4 patients had normal immunization responses, and the fourth has started immunizations. Vector insertion sites showed no evidence of clonal expansion. One patient who presented with cytomegalovirus infection received a second infusion of gene-corrected cells to achieve T-cell immunity sufficient for viral clearance. Autoimmune hemolytic anemia developed in 4 patients 4 to 11 months after infusion; this condition resolved after reconstitution of T-cell immunity. All 10 patients were healthy at the time of this report.

conclusionsInfusion of lentiviral gene-corrected autologous CD34+ cells, preceded by pharmacologically targeted low-exposure busulfan, in infants with newly diagnosed ART-SCID resulted in genetically corrected and functional T and B cells. (Funded by the California Institute for Regenerative Medicine and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03538899.).

Indexed as

Genetic TherapySevere Combined ImmunodeficiencyAntigens, CD34B-LymphocytesBusulfanDNA-Binding ProteinsDNA Repair EnzymesEndonucleasesGenetic VectorsHumansImmunoglobulin MInfantLentivirusT-LymphocytesTransplantation, AutologousAntigens, CD34BusulfanDCLRE1C protein, humanDNA-Binding ProteinsDNA Repair EnzymesEndonucleasesImmunoglobulin M

Identifiers

PMID36546626
PMCPMC9884487
OpenAlexW4313236943

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Registered trials

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.