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A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders

Tucci, Francesca, Galimberti, Stefania, Naldini, Luigi, Valsecchi, Maria Grazia, Aiuti, Alessandro·2022·Nature Communications
DOI 10.1038/s41467-022-28762-2PMC PMC8921234

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Abstract

Ex-vivo gene therapy (GT) with hematopoietic stem and progenitor cells (HSPCs) engineered with integrating vectors is a promising treatment for monogenic diseases, but lack of centralized databases is hampering an overall outcomes assessment. Here we aim to provide a comprehensive assessment of the short and long term safety of HSPC-GT from trials using different vector platforms. We review systematically the literature on HSPC-GT to describe survival, genotoxicity and engraftment of gene corrected cells. From 1995 to 2020, 55 trials for 14 diseases met inclusion criteria and 406 patients with primary immunodeficiencies (55.2%), metabolic diseases (17.0%), haemoglobinopathies (24.4%) and bone marrow failures (3.4%) were treated with gammaretroviral vector (γRV) (29.1%), self-inactivating γRV (2.2%) or lentiviral vectors (LV) (68.7%). The pooled overall incidence rate of death is 0.9 per 100 person-years of observation (PYO) (95% CI = 0.37–2.17). There are 21 genotoxic events out of 1504.02 PYO, which occurred in γRV trials (0.99 events per 100 PYO, 95% CI = 0.18–5.43) for primary immunodeficiencies. Pooled rate of engraftment is 86.7% (95% CI = 67.1–95.5%) for γRV and 98.7% (95% CI = 94.5–99.7%) for LV HSPC-GT (p = 0.005). Our analyses show stable reconstitution of haematopoiesis in most recipients with superior engraftment and safer profile in patients receiving LV-transduced HSPCs.

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Fig. 1 PRISMA diagram detailing the search strategy. PRISMA diagram detailing the search strategy of articles for inclusion in the meta-analysis.
Fig. 1 PRISMA diagram detailing the search strategy. PRISMA diagram detailing the search strategy of articles for inclusion in the meta-analysis.CC BY · PubMed Central
Fig. 2 Forest plot of the incidence rate of mortality by vector type, i.e., (A) γRV, (B) LV, (C) SIN-γRV, and overall. The squares indicate the incidence rate of mortality and their size reflects the study sample size, while the horizontal lines represent 95% Confidence Intervals (CI). The diamond denotes the summary effect size from the random-effects model for all or subgroups of studies (from a meta-regression model), and the width of the diamond depicts the overall 95% CI. The indices of heterogeneity (I2 and τ2) refer to the overall analysis or to the single subgroups, and pLRT is the p value for the test of residual heterogeneity, while pQM refers to the test on vector type as moderator. All tests were two-tailed. Source data are provided as a Source Data file.
Fig. 2 Forest plot of the incidence rate of mortality by vector type, i.e., (A) γRV, (B) LV, (C) SIN-γRV, and overall. The squares indicate the incidence rate of mortality and their size reflects the study sample size, while the horizontal lines represent 95% Confidence Intervals (CI). The diamond denotes the summary effect size from the random-effects model for all or subgroups of studies (from a meta-regression model), and the width of the diamond depicts the overall 95% CI. The indices of heterogeneity (I2 and τ2) refer to the overall analysis or to the single subgroups, and pLRT is the p value for the test of residual heterogeneity, while pQM refers to the test on vector type as moderator. All tests were two-tailed. Source data are provided as a Source Data file.CC BY · PubMed Central
Fig. 3 Forest plot of the incidence rate of genotoxicity by vector type, i.e., (A) γRV, (B) LV, (C) SIN-γRV, and overall. The squares indicate the incidence rate of genotoxicity and their size reflects the study sample size, while the horizontal lines represent 95% Confidence Intervals (CI). The diamond denotes the summary effect size from the random-effects model for all or subgroups of studies (from a meta-regression model), and the width of the diamond depicts the overall 95% CI. The indices of heterogeneity (I2 and τ2) refer to the overall analysis or to the single subgroups, and pLRT is the p-value for the test of residual heterogeneity, while pQM refers to the test on vector type as moderator. All tests were two-tailed. Source data are provided as a Source Data file.
Fig. 3 Forest plot of the incidence rate of genotoxicity by vector type, i.e., (A) γRV, (B) LV, (C) SIN-γRV, and overall. The squares indicate the incidence rate of genotoxicity and their size reflects the study sample size, while the horizontal lines represent 95% Confidence Intervals (CI). The diamond denotes the summary effect size from the random-effects model for all or subgroups of studies (from a meta-regression model), and the width of the diamond depicts the overall 95% CI. The indices of heterogeneity (I2 and τ2) refer to the overall analysis or to the single subgroups, and pLRT is the p-value for the test of residual heterogeneity, while pQM refers to the test on vector type as moderator. All tests were two-tailed. Source data are provided as a Source Data file.CC BY · PubMed Central
Fig. 4 Aalen-Johansen crude cumulative incidence rate of genotoxicity (A) overall and stratified by (B) vector type and (C) disease using γRV. The result of the Gray test (two-tailed) is also reported. Source data are provided as a Source Data file.
Fig. 4 Aalen-Johansen crude cumulative incidence rate of genotoxicity (A) overall and stratified by (B) vector type and (C) disease using γRV. The result of the Gray test (two-tailed) is also reported. Source data are provided as a Source Data file.CC BY · PubMed Central
Fig. 5 Forest plot of the rate of engraftment by vector type, i.e., (A) γRV, (B) LV, (C) SIN-γRV, and overall. The squares indicate the rate of engraftment and their size reflects the study sample size, while the horizontal lines represent 95% Confidence Intervals (CI). The diamond denotes the summary effect size from the random-effects model for all or subgroups of studies (from a meta-regression model), and the width of the diamond depicts the overall 95% CI. The indices of heterogeneity (I2 and τ2) refer to the overall analysis or to the single subgroups, and pLRT is the p value for the test of residual heterogeneity, while pQM refers to the test on vector type as moderator. All tests were two-tailed. Source data are provided as a Source Data file.
Fig. 5 Forest plot of the rate of engraftment by vector type, i.e., (A) γRV, (B) LV, (C) SIN-γRV, and overall. The squares indicate the rate of engraftment and their size reflects the study sample size, while the horizontal lines represent 95% Confidence Intervals (CI). The diamond denotes the summary effect size from the random-effects model for all or subgroups of studies (from a meta-regression model), and the width of the diamond depicts the overall 95% CI. The indices of heterogeneity (I2 and τ2) refer to the overall analysis or to the single subgroups, and pLRT is the p value for the test of residual heterogeneity, while pQM refers to the test on vector type as moderator. All tests were two-tailed. Source data are provided as a Source Data file.CC BY · PubMed Central

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Citations

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Research works printed but not linked: 81

  1. Ferrari, G., Thrasher, A. J. & Aiuti, A. Gene therapy using haematopoietic stem and progenitor cells. Nat. Rev. Genet. https://doi.org/10.1038/s41576-020-00298-5 (2020). · DOI
  2. Tucci, F., Scaramuzza, S., Aiuti, A. & Mortellaro, A. Update on Clinical Ex vivo hematopoietic stem cell gene therapy for inherited monogenic diseases. Mol. Ther. https://doi.org/10.1016/j.ymthe.2020.11.020 (2020). · DOI
  3. Cavazzana, M., Bushman, F. D., Miccio, A., Andre-Schmutz, I. & Six, E. Gene therapy targeting haematopoietic stem cells for inherited diseases: progress and challenges. Nat. Rev. Drug Disco. 18, 447–462 (2019). · DOI
  4. Slatter, M. A. et al. Treosulfan and fludarabine conditioning for hematopoietic stem cell transplantation in children with primary immunodeficiency: UK experience. Biol. Blood Marrow Transpl. 24, 529–536 (2018). · DOI
  5. Hassan, A. et al. Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency. Blood 120, 3615–3624 (2012). · DOI
  6. Fox, T. A. et al. Successful outcome following allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency. Blood 131, 917–931 (2018). · DOI
  7. Albert, M. H. et al. Allogeneic stem cell transplantation in adolescents and young adults with primary immunodeficiencies. J. Allergy Clin. Immunol. Pr. 6, 298–301 e292 (2018). · DOI
  8. Pai, S. Y. et al. Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N. Engl. J. Med 371, 434–446 (2014). · DOI
  9. Murillo-Sanjuan, L. et al. Survival and toxicity outcomes of hematopoietic stem cell transplantation for pediatric patients with Fanconi anemia: a unified multicentric national study from the Spanish Working Group for Bone Marrow Transplantation in Children. Bone Marrow Transplant. https://doi.org/10.1038/s41409-020-01172-y (2020). · DOI
  10. Boucher, A. A. et al. Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: the largest single-institution cohort report. Orphanet J. Rare Dis. 10, 94 (2015). · DOI
  11. Raymond, G. V. et al. Survival and functional outcomes in boys with cerebral adrenoleukodystrophy with and without hematopoietic stem cell transplantation. Biol. Blood Marrow Transpl. 25, 538–548 (2019). · DOI · Paper page
  12. Aldenhoven, M. et al. Hematopoietic cell transplantation for mucopolysaccharidosis patients is safe and effective: results after implementation of international guidelines. Biol. Blood Marrow Transpl. 21, 1106–1109 (2015). · DOI
  13. Strocchio, L. & Locatelli, F. Hematopoietic stem cell transplantation in Thalassemia. Hematol. Oncol. Clin. North Am. 32, 317–328 (2018). · DOI
  14. Gluckman, E. et al. Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation. Blood 129, 1548–1556 (2017). · DOI
  15. Mayor, P. C. et al. Cancer in primary immunodeficiency diseases: Cancer incidence in the United States Immune Deficiency Network Registry. J. Allergy Clin. Immunol. 141, 1028–1035 (2018). · DOI
  16. Hauck, F., Gennery, A. R. & Seidel, M. G. Editorial: The relationship between cancer predisposition and primary immunodeficiency. Front. Immunol. 10, 1781 (2019). · DOI
  17. Ferrua, F. et al. Lentiviral haemopoietic stem/progenitor cell gene therapy for treatment of Wiskott-Aldrich syndrome: interim results of a non-randomised, open-label, phase 1/2 clinical study. Lancet Haematol. 6, e239–e253 (2019). · DOI
  18. Marktel, S. et al. Intrabone hematopoietic stem cell gene therapy for adult and pediatric patients affected by transfusion-dependent ss-thalassemia. Nat. Med. 25, 234–241 (2019). · DOI
  19. Bushman, F. D. Retroviral insertional mutagenesis in humans: evidence for four genetic mechanisms promoting expansion of cell clones. Mol. Ther. 28, 352–356 (2020). · DOI
  20. Walters M. C. et al. Exploring the drivers of potential clinical benefit in initial patients treated in the Hgb-206 Study of Lentiglobin for Sickle Cell Disease (SCD) Gene Therapy. Blood 2061 (2019). https://doi.org/10.1182/blood-2019-128814 · DOI
  21. Jones, R. R. & DeBaun, M. R. Leukemia after gene therapy for sickle cell disease: insertional mutagenesis, busulfan, both, or neither. Blood 138, 942–947 (2021). · DOI
  22. Servick, K. Gene therapy clinical trial halted as cancer risk surfaces. https://doi.org/10.1126/science.abl8782 (2021). · DOI
  23. Palchaudhuri, R. et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat. Biotechnol. 34, 738–745 (2016). · DOI
  24. Kwon, H. S. et al. Anti-human CD117 antibody-mediated bone marrow niche clearance in nonhuman primates and humanized NSG mice. Blood 133, 2104–2108 (2019). · DOI
  25. Hsieh, M. M. et al. Myelodysplastic syndrome unrelated to lentiviral vector in a patient treated with gene therapy for sickle cell disease. Blood Adv. 4, 2058–2063 (2020). · DOI · Paper page
  26. Sokolic, R. et al. Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency. Blood 118, 2688–2694 (2011). · DOI
  27. Regan, S., Yang, X., Finnberg, N. K., El-Deiry, W. S. & Pu, J. J. Occurrence of acute myeloid leukemia in hydroxyurea-treated sickle cell disease patient. Cancer Biol. Ther. 20, 1389–1397 (2019). · DOI
  28. Aiuti, A. & Naldini, L. Safer conditioning for blood stem cell transplants. Nat. Biotechnol. 34, 721–723 (2016). · DOI
  29. Agarwal, R. et al. Toxicity-Free Hematopoietic Stem Cell Engraftment Achieved with Anti-CD117 Monoclonal Antibody Conditioning. Biol. Blood Marrow Transpl. 25, S92 (2019). · DOI
  30. McGrath, E., Chabannon, C., Terwel, S., Bonini, C. & Kuball, J. Opportunities and challenges associated with the evaluation of chimeric antigen receptor T cells in real-life. Curr. Opin. Oncol. 32, 427–433 (2020). · DOI
  31. Candotti, F. et al. Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans. Blood 120, 3635–3646 (2012). · DOI
  32. Shaw, K. L. et al. Clinical efficacy of gene-modified stem cells in adenosine deaminase-deficient immunodeficiency. J. Clin. Invest. 127, 1689–1699 (2017). · DOI
  33. Aiuti, A. et al. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science 296, 2410–2413 (2002). · DOI · Paper page
  34. Aiuti, A. et al. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N. Engl. J. Med. 360, 447–458 (2009). · DOI
  35. Cicalese, M. P. et al. Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency. Blood 128, 45–54 (2016). · DOI
  36. Cicalese M. P. et al. Retroviral gene therapy for the treatment of ADA-SCID: long-term follow up and first case of T-cell acute leukaemia due to insertional mutagenesis. HemaSphere 5, https://doi.org/10.1097/hs9.0000000000000566 (2021). · DOI
  37. Otsu, M. et al. Outcomes in two Japanese adenosine deaminase-deficiency patients treated by stem cell gene therapy with no cytoreductive conditioning. J. Clin. Immunol. 35, 384–398 (2015). · DOI
  38. Gaspar, H. B. et al. Hematopoietic stem cell gene therapy for adenosine deaminase-deficient severe combined immunodeficiency leads to long-term immunological recovery and metabolic correction. Sci. Transl. Med. 3, 97ra80 (2011). · DOI
  39. Gaspar, H. B. et al. Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning. Mol. Ther. 14, 505–513 (2006). · DOI
  40. Kohn, D. B. et al. T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates. Nat. Med. 4, 775–780 (1998). · DOI
  41. Schmidt, M. et al. Clonality analysis after retroviral-mediated gene transfer to CD34+ cells from the cord blood of ADA-deficient SCID neonates. Nat. Med. 9, 463–468 (2003). · DOI
  42. Boztug, K. et al. Stem-cell gene therapy for the Wiskott-Aldrich syndrome. N. Engl. J. Med. 363, 1918–1927 (2010). · DOI · Paper page
  43. Malech, H. L. et al. Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease. Proc. Natl Acad. Sci. USA 94, 12133–12138 (1997). · DOI
  44. Siler, U. et al. Successful combination of sequential gene therapy and rescue Allo-HSCT in Two Children with X-CGD - Importance of Timing. Curr. Gene Ther. 15, 416–427 (2015). · DOI
  45. Ott, M. G. et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat. Med. 12, 401–409 (2006). · DOI · Paper page
  46. Kang, E. M. et al. Retrovirus gene therapy for X-linked chronic granulomatous disease can achieve stable long-term correction of oxidase activity in peripheral blood neutrophils. Blood 115, 783–791 (2010). · DOI
  47. Kang, H. J. et al. Retroviral gene therapy for X-linked chronic granulomatous disease: results from phase I/II trial. Mol. Ther. 19, 2092–2101 (2011). · DOI
  48. Uchiyama, T. et al. Insertional Oncogenesis in X-CGD Patient after MFGS Retroviral Vector-Mediated Gene Therapy. Mol. Ther. 27, 9 (2019).
  49. Hacein-Bey-Abina, S. et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302, 415–419 (2003). · DOI · Paper page
  50. Hacein-Bey-Abina, S. et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N. Engl. J. Med. 363, 355–364 (2010). · DOI
  51. Ginn, S. L. et al. Treatment of an infant with X-linked severe combined immunodeficiency (SCID-X1) by gene therapy in Australia. Med. J. Aust. 182, 458–463 (2005). · DOI
  52. Six, E. et al. LMO2 Associated Clonal T Cell Proliferation 15 Years After Gamma-Retrovirus Mediated Gene Therapy for SCIDX1. Mol. Ther. 25, 347–348 (2017).
  53. Gaspar, H. B. et al. Long-term persistence of a polyclonal T cell repertoire after gene therapy for X-linked severe combined immunodeficiency. Sci. Transl. Med. 3, 97ra79 (2011). · DOI
  54. Chinen, J. et al. Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency. Blood 110, 67–73 (2007). · DOI
  55. Thrasher, A. J. et al. Failure of SCID-X1 gene therapy in older patients. Blood 105, 4255–4257 (2005). · DOI
  56. Gaspar, H. B. et al. Immunological and Metabolic Correction After Lentiviral Vector Mediated Haematopoietic Stem Cell Gene Therapy for ADA Deficiency. Mol. Ther. 22, S106 (2014). · DOI
  57. Kohn, D. B. et al. Lentiviral Gene Therapy with Autologous Hematopoietic Stem and Progenitor Cells (HSPCs) for the Treatment of Severe Combined Immune Deficiency Due to Adenosine Deaminase Deficiency (ADA-SCID): Two Year Follow-Up Results. Mol. Ther. 28, 554–555 (2020).
  58. Scaramuzza, S. et al. Clinical Outcomes from a Phase I/II Gene Therapy Trial for Patients affected by Severe Transfusion Dependent Beta-Thalassemia: Two Years Follow Up. Mol. Ther. 28, 169 (2020).
  59. Lal, A. et al. Northstar-3: Interim Results from a Phase 3 Study Evaluating Lentiglobin Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia and Either a β0 or IVS-I-110 Mutation at Both Alleles of the HBB Gene. Blood 134, 815 (2019). · DOI
  60. Barshop, B. et al. Hematopoietic Stem Cell Gene Therapy for Cystinosis: Initial Results from a Phase I/II Clinical Trial. Mol. Ther. 28, 233 (2020).
  61. Khan, A. et al. Lentivirus-mediated gene therapy for Fabry disease. Nat. Commun. 12, 1178 (2021). · DOI
  62. Adair, J. E. et al. Lessons Learned from Two Decades of Clinical Trial Experience in Gene Therapy for Fanconi Anemia. Curr. Gene Ther. 16, 338–348 (2017). · DOI
  63. Rio, P. et al. Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia. Nat. Med. 25, 1396–1401 (2019). · DOI
  64. Río, P. et al. Updated Results of a European Gene Therapy Trial in Fanconi Anemia Patients, Subtype A. Mol. Ther. 28, 57 (2020).
  65. Czechowicz, A. et al. Changing the Natural History of Fanconi Anemia Complementation Group-À with Gene Therapy: Early Results of U.S. Phase I Study of Lentiviral-Mediated Ex-Vivo FANCA Gene Insertion in Human Stem and Progenitor Cells. Biol. Blood Marrow Transplant 26, S39–S40 (2020). · DOI
  66. Kohn, D. B. et al. Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Initial Results from the First Treated Patient. Mol. Ther. 28, 56 (2020).
  67. Biffi, A. et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 341, 1233158 (2013). · DOI · Paper page
  68. Fumagalli, F. et al. In 16th Annual WORLD Symposium, Orlando USA (2020).
  69. Kinsella, J. B. K. et al. Preliminary outcomes of haematopoietic stem cell gene therapy in a patient with Mucopolysaccharidosis IIIA. Mol. Ther. 28, 231–232 (2020).
  70. Tisdale, J. F. et al. Resolution of Sickle Cell Disease (SCD) Manifestations in Patients Treated with Lentiglobin Gene Therapy: Updated Results from the Phase 1/2 HGB-206 Group C Study. Mol. Ther. 28, 553 (2020).
  71. Esrick, E. B. et al. Validation of BCL11A As Therapeutic Target in Sickle Cell Disease: Results from the Adult Cohort of a Pilot/Feasibility Gene Therapy Trial Inducing Sustained Expression of Fetal Hemoglobin Using Post-Transcriptional Gene Silencing. Blood 134: https://doi.org/10.1182/blood-2019-132745 (2019). · DOI
  72. Aiuti, A. et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science 341, 1233151 (2013). · DOI · Paper page
  73. Hacein-Bey Abina, S. et al. Outcomes following gene therapy in patients with severe Wiskott-Aldrich syndrome. JAMA 313, 1550–1563 (2015). · DOI · Paper page
  74. Magnani, A. et al. Long-Term Follow-Up Study after Lentiviral Hematopoietic Stem/Progenitor Cell Gene Therapy for Wiskott-Aldrich Syndrome. Mol. Ther. 28, 58 (2020).
  75. Morris, E. C. et al. Gene therapy for Wiskott-Aldrich syndrome in a severely affected adult. Blood 130, 1327–1335 (2017). · DOI
  76. Labrosse, R. et al. Outcome of Hematopoietic Stem Cell Gene Therapy for Wiskott-Aldrich Syndrome. Blood 134, 4629 (2019). · DOI
  77. Aubourg, P. et al. Continuing Clinical Efficacy and ALDP Gene Expression 5–10 Years after Lentiviral LV-Based CD34+ Cell Gene Therapy in Patients with X-linked Adrenoleukodystrophy (X-ALD). Mol. Ther. 28, 274 (2020).
  78. Kohn, D. B. et al. Lentiviral gene therapy for X-linked chronic granulomatous disease. Nat. Med 26, 200–206 (2020). · DOI · Paper page
  79. De Ravin, S. S. et al. Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency. Sci. Transl. Med 8, 335ra357 (2016). · DOI · Paper page
  80. De Ravin, S. S. et al. Enhanced Transduction Lentivector Gene Therapy for Treatment of Older Patients with X-Linked Severe Combined Immunodeficiency. Blood 134, 608 (2019). · DOI
  81. Mamcarz, E. et al. Lentiviral Gene Therapy with Low Dose Busulfan for Infants with X-SCID Results in the Development of a Functional Normal Immune System: Interim Results of an Ongoing Phase I/II Clinical Study. Blood 134, 608 (2019). · DOI

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Metadata

Authors
Tucci, F., Galimberti, S., Naldini, L., Valsecchi, M. G., & Aiuti, A.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2022-03-14
Volume
13
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-022-28762-2
PMC
PMC8921234
Cited by
145
References
12
Language
en
Licence
Funders
Fondazione Telethon (SR-TIGET core grant)

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