Evidence map›Paper›PMID 24256635›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014

Preclinical demonstration of lentiviral vector-mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency.

Denise A Carbonaro, Lin Zhang, Xiangyang Jin, Claudia Montiel-Equihua, Sabine Geiger, Marlene Carmo, Aaron Cooper, Lynette Fairbanks, Michael L Kaufman, Neil J Sebire and 11 more

3 registry-linked trialsOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
5.8field-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.

NCT01852071 phase1 / phase2completednot on this map

Autologous Transplantation of Bone Marrow CD34+ Stem/Progenitor Cells After Addition of a Normal Human ADA Complementary DNA (cDNA) by the EFS-ADA Lentiviral Vector for Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID)

TypeinterventionalSponsorUniversity of California, Los AngelesRan2013 to 2018Enrolled46ConditionsADA-SCIDArmsInfusion of autologous EFS-ADA LV CD34+ (OTL-101), busulfan, PEG-ADA ERT
NCT02999984 phase1 / phase2completednot on this mapstarted 2016, after this paper: background citation

Efficacy and Safety of Cryopreserved Formulation of Autologous CD34+ Hematopoietic Stem Cells Transduced Ex Vivo With Elongation Factor 1 Alpha Shortened (EFS) Lentiviral Vector Encoding for Human ADA Gene in Subjects With Severe Combined Immunodeficiency Due to ADA Deficiency

TypeinterventionalSponsorUniversity of California, Los AngelesRan2016 to 2019Enrolled10ConditionsSevere Combined Immunodeficiency Due to ADA DeficiencyArmsInfusion of autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101), busulfan, PEG-ADA ERT
NCT05432310 phase1 / phase2active not recruitingnot on this mapstarted 2023, after this paper: background citation

Efficacy and Safety of Cryopreserved Autologous Mobilized Peripheral Blood CD34+ HSPCs Transduced Ex Vivo With the EFS-ADA Lentiviral Vector in Patients With Severe Combined Immune Deficiency Due To Adenosine Deaminase Deficiency

TypeinterventionalSponsorUniversity of California, Los AngelesRan2023 to 2027Enrolled20ConditionsAdenosine Deaminase Severe Combined Immune DeficiencyArmsA cryopreserved formulation of autologous mPB CD34+ hematopoietic stem and progenitor cells transduced ex vivo with the EFS-ADA lentiviral vector encoding the human ADA enzyme
3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 80 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Quantifying the mutational landscape of retroviral and lentiviral vectors in gene therapy patients.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  5. 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
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Gene delivery using AAV8Molecular therapy. Methods & clinical development · 2021
    Article
  16. Article
  17. Article
  18. Review
  19. Busulfan Pharmacokinetics in Adenosine Deaminase-Deficient Severe Combined Immunodeficiency Gene Therapy.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2020
    Article
  20. Article
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

21 authors at 4 institutions in 2 countries.

Denise A CarbonaroDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA.
Lin ZhangCentre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, UK.
Xiangyang JinDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA.
Claudia Montiel-EquihuaCentre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, UK.
Sabine GeigerDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA.
Marlene CarmoCentre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, UK.
Aaron CooperDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA.
Lynette FairbanksPurine Research Laboratory, St Thomas Hospital, London, UK.
Michael L KaufmanDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA.
Neil J SebireDepartment of Paediatric Pathology, Great Ormond Street Hospital, London, UK.
Roger P HollisDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA.
Michael P BlundellCentre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, UK.
Shantha SenadheeraDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA.
Pei-Yu FuDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA.
Arineh SahaghianDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA.
Rebecca Y ChanDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA.
Xiaoyan WangDepartment of Medicine Statistics Core, University of California, Los Angeles, California, USA.
Kenneth CornettaDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Adrian J ThrasherCentre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, UK.
Donald B KohnDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA; Department of Pediatrics (Hematology/Oncology), Mattel Children's Hospital, University of California, Los Angeles, California, USA.
H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, UK. Electronic address: h.gaspar@ucl.ac.uk.
University of California, Los Angeles · USUniversity College London · GBIndiana University – Purdue University Indianapolis · USSt Thomas' Hospital · GB

Funding

UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
Transduction of Human Stem and Progenitor CellsP01HL073104 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOHN, DONALD B · 2003 to 2013
$18.3M
EFS-ADA Lentiviral Vector Transduction of Bone Marrow CD34+ Cells for ADA-SCIDU01AI100801 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOHN, DONALD B · 2012 to 2016
$3.2M
In Vivo ADA Gene Delivery for the Treatment of SCIDR01AI074043 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOHN, DONALD B · 2007 to 2011
$2.3M
Medical Research Council G0600773Medical Research Council G0802483NHLBI NIH HHS 2P01 HL073104NHLBI NIH HHS HHSN268201000051CNHLBI NIH HHS P01 HL073104NIAID NIH HHS R01 AI074043NIAID NIH HHS U01 AI100801NIGMS NIH HHS T32 GM007185Wellcome Trust
6 · The paper itself

Abstract

Gene transfer into autologous hematopoietic stem cells by γ-retroviral vectors (gRV) is an effective treatment for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID). However, current gRV have significant potential for insertional mutagenesis as reported in clinical trials for other primary immunodeficiencies. To improve the efficacy and safety of ADA-SCID gene therapy (GT), we generated a self-inactivating lentiviral vector (LV) with a codon-optimized human cADA gene under the control of the short form elongation factor-1α promoter (LV EFS ADA). In ADA(-/-) mice, LV EFS ADA displayed high-efficiency gene transfer and sufficient ADA expression to rescue ADA(-/-) mice from their lethal phenotype with good thymic and peripheral T- and B-cell reconstitution. Human ADA-deficient CD34(+) cells transduced with 1-5 × 10(7) TU/ml had 1-3 vector copies/cell and expressed 1-2x of normal endogenous levels of ADA, as assayed in vitro and by transplantation into immune-deficient mice. Importantly, in vitro immortalization assays demonstrated that LV EFS ADA had significantly less transformation potential compared to gRV vectors, and vector integration-site analysis by nrLAM-PCR of transduced human cells grown in immune-deficient mice showed no evidence of clonal skewing. These data demonstrated that the LV EFS ADA vector can effectively transfer the human ADA cDNA and promote immune and metabolic recovery, while reducing the potential for vector-mediated insertional mutagenesis.

Indexed as

Adenosine DeaminaseAgammaglobulinemiaAnimalsB-LymphocytesCells, CulturedDisease Models, AnimalFemaleGenetic VectorsHEK293 CellsHT29 CellsHumansLentivirusMaleMiceMice, Inbred C57BLPeptide Elongation Factor 1Adenosine DeaminasePeptide Elongation Factor 1

Identifiers

PMID24256635
PMCPMC3944341
OpenAlexW2025735261

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.