REFERENCES

1. Dvorak CC, Haddad E, Heimall J, et al. The diagnosis of severe combined immunodeficiency (SCID): The Primary Immune Deficiency Treatment Consortium (PIDTC) 2022 definitions. J Allergy Clin Immunol. 2023;151:539-46.

2. Gaspar HB, Gilmour KC, Jones AM. Severe combined immunodeficiency--molecular pathogenesis and diagnosis. Arch Dis Child. 2001;84:169-73.

3. Heimall J, Cowan MJ. Long term outcomes of severe combined immunodeficiency: therapy implications. Expert Rev Clin Immunol. 2017;13:1029-40.

4. Albin S, Cunningham-Rundles C. An update on the use of immunoglobulin for the treatment of immunodeficiency disorders. Immunotherapy. 2014;6:1113-26.

5. Tasher D, Dalal I. The genetic basis of severe combined immunodeficiency and its variants. Appl Clin Genet. 2012;5:67-80.

6. Aranda CS, Gouveia‐pereira MP, Da Silva CJM, et al. Severe combined immunodeficiency diagnosis and genetic defects. Immunol Rev. 2024;322:138-47.

7. Cirillo E, Giardino G, Gallo V, et al. Severe combined immunodeficiency - an update. Ann N Y Acad Sci. 2015;1356:90-106.

8. Bradford KL, Moretti FA, Carbonaro-sarracino DA, Gaspar HB, Kohn DB. Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations. J Clin Immunol. 2017;37:626-37.

9. Wahlstrom JT, Dvorak CC, Cowan MJ. Hematopoietic stem cell transplantation for severe combined immunodeficiency. Curr Pediatr Rep. 2015;3:1-10.

10. Haddad E, Hoenig M. Hematopoietic stem cell transplantation for severe combined immunodeficiency (SCID). Front. Pediatr. 2019;7:481.

11. Buckley RH. A historical review of bone marrow transplantation for immunodeficiencies. J Allergy Clin Immunol. 2004;113:793-800.

12. Lidonnici MR, Aprile A, Frittoli MC, et al. Plerixafor and G-CSF combination mobilizes hematopoietic stem and progenitors cells with a distinct transcriptional profile and a reducedin vivo homing capacity compared to plerixafor alone. Haematologica. 2017;102:e120-4.

13. Bendall LJ, Bradstock KF. G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilizing agent. Cytokine Growth Factor Rev. 2014;25:355-67.

14. Nakamura N, Jo T, Arai Y, et al. Benefits of plerixafor for mobilization of peripheral blood stem cells prior to autologous transplantation: a dual-center retrospective cohort study. Cytotherapy. 2023;25:773-81.

15. Ciurea SO, Andersson BS. Busulfan in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:523-36.

16. John T, Czechowicz A. Clinical hematopoietic stem cell-based gene therapy. Mol Ther. 2025;33:2663-78.

17. Ferrari G, Thrasher AJ, Aiuti A. Gene therapy using haematopoietic stem and progenitor cells. Nat Rev Genet. 2020;22:216-34.

18. Frangoul H, Locatelli F, Sharma A, et al. Exagamglogene autotemcel for severe sickle cell disease. N Engl J Med. 2024;390:1649-62.

19. Schimmer J, Breazzano S. Investor outlook: rising from the ashes; GSK’s European approval of strimvelis for ADA-SCID. Hum Gene Ther Clin Dev. 2016;27:57-61.

20. Zhang Z, Thrasher AJ, Zhang F. Gene therapy and genome editing for primary immunodeficiency diseases. Genes Dis. 2020;7:38-51.

21. Bulcha JT, Wang Y, Ma H, Tai PWL, Gao G. Viral vector platforms within the gene therapy landscape. Sig Transduct Target Ther. 2021;6:53.

22. Migliavacca M, Barzaghi F, Fossati C, et al. Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency. Nat Med. 2024;30:488-97.

23. Cesana D, Cicalese MP, Calabria A, et al. A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID. Nat Commun. 2024;15:3662.

24. Hacein-bey-abina S, Hauer J, Lim A, et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2010;363:355-64.

25. Howe SJ, Mansour MR, Schwarzwaelder K, et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Investig. 2008;118:3143-50.

26. Braun CJ, Boztug K, Paruzynski A, et al. Gene therapy for Wiskott-Aldrich syndrome - long-term efficacy and genotoxicity. Sci Transl Med. 2014;6.

27. Biasco L, Baricordi C, Aiuti A. Retroviral integrations in gene therapy trials. Mol Ther. 2012;20:709-16.

28. Montini E, Cesana D, Schmidt M, et al. The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy. J Clin Investig. 2009;119:964-75.

29. Modlich U, Navarro S, Zychlinski D, et al. Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectors. Mol Ther. 2009;17:1919-28.

30. Bokhoven M, Stephen SL, Knight S, et al. Insertional gene activation by lentiviral and gammaretroviral vectors. J Virol. 2009;83:283-94.

31. Kohn DB, Booth C, Shaw KL, et al. Autologous ex vivo lentiviral gene therapy for adenosine deaminase deficiency. N Engl J Med. 2021;384:2002-13.

32. Carbonaro DA, Zhang L, Jin X, et al. Preclinical demonstration of lentiviral vector-mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency. Mol Ther. 2014;22:607-22.

33. Zhou S, Mody D, Deravin SS, et al. A self-inactivating lentiviral vector for SCID-X1 gene therapy that does not activate LMO2 expression in human T cells. Blood. 2010;116:900-8.

34. Poletti V, Charrier S, Corre G, et al. Preclinical development of a lentiviral vector for gene therapy of X-linked severe combined immunodeficiency. Mol Ther Methods Clin Dev. 2018;9:257-69.

35. Mamcarz E, Zhou S, Lockey T, et al. Lentiviral gene therapy combined with low-dose busulfan in infants with SCID-X1. N Engl J Med. 2019;380:1525-34.

36. Kuo TC, Schlissel MS. Mechanisms controlling expression of the RAG locus during lymphocyte development. Curr Opin Immunol. 2009;21:173-8.

37. Gilioli G, Lankester AC, De Kivit S, Staal FJ, Ott De Bruin LM. Gene therapy strategies for RAG1 deficiency: challenges and breakthroughs. Immunol Lett. 2024;270:106931.

38. Malu S, De Ioannes P, Kozlov M, et al. Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs. J Exp Med. 2012;209:955-63.

39. Mansilla-Soto J, Cortes P. VDJ recombination: Artemis and its in vivo role in hairpin opening. J Exp Med. 2003;197:543-7.

40. Nishana M, Raghavan SC. Role of recombination activating genes in the generation of antigen receptor diversity and beyond. Immunology. 2012;137:271-81.

41. Lagresle-peyrou C, Benjelloun F, Hue C, et al. Restoration of human B-cell differentiation into NOD-SCID mice engrafted with gene-corrected CD34+ cells isolated from Artemis or RAG1-deficient patients. Mol Ther. 2008;16:396-403.

42. Garcia-perez L, Van Eggermond M, Van Roon L, et al. Successful preclinical development of gene therapy for recombinase-activating gene-1-deficient SCID. Mol Ther Methods Clin Dev. 2020;17:666-82.

43. Pike-overzet K, Rodijk M, Ng Y, et al. Correction of murine Rag1 deficiency by self-inactivating lentiviral vector-mediated gene transfer. Leukemia. 2011;25:1471-83.

44. Sorel N, Díaz-pascual F, Bessot B, et al. Restoration of T and B cell differentiation after RAG1 gene transfer in human RAG1 defective hematopoietic stem cells. Biomedicines. 2024;12:1495.

45. Montini E, Naldini L, Booth C, Kohn DB, Aiuti A. Balancing efficacy and safety in lentiviral vector-mediated hematopoietic stem cell gene therapy. Mol Ther. 2025;33:6-8.

46. Staal FJ, Pike-overzet K, De Kivit S, et al. Safety and efficacy of gene therapy for RAG1-deficient SCID. Mol Ther. 2025;33:1869-70.

47. Jones JM, Gellert M. The taming of a transposon: V(D)J recombination and the immune system. Immunol Rev. 2004;200:233-48.

48. Schwarzer A, Talbot SR, Selich A, et al. Predicting genotoxicity of viral vectors for stem cell gene therapy using gene expression-based machine learning. Mol Ther. 2021;29:3383-97.

49. Duncan CN, Bledsoe JR, Grzywacz B, et al. Hematologic cancer after gene therapy for cerebral adrenoleukodystrophy. N Engl J Med. 2024;391:1287-301.

50. Multhaup M, Karlen AD, Swanson DL, et al. Cytotoxicity associated with Artemis overexpression after lentiviral vector-mediated gene transfer. Hum Gene Ther. 2010;21:865-75.

51. Mostoslavsky G, Fabian AJ, Rooney S, Alt FW, Mulligan RC. Complete correction of murine Artemis immunodeficiency by lentiviral vector-mediated gene transfer. Proc. Natl. Acad. Sci. U.S.A. 2006;103:16406-11.

52. Benjelloun F, Garrigue A, Demerens-de Chappedelaine C, et al. Stable and functional lymphoid reconstitution in Artemis-deficient mice following lentiviral Artemis gene transfer into hematopoietic stem Cells. Mol Ther. 2008;16:1490-9.

53. Cowan MJ, Yu J, Facchino J, et al. Lentiviral gene therapy for Artemis-deficient SCID. N Engl J Med. 2022;387:2344-55.

54. Liu D, Cao D, Han R. Recent advances in therapeutic gene-editing technologies. Mol Ther. 2025;33:2619-44.

55. Liu X, Li G, Liu Y, Zhou F, Huang X, Li K. Advances in CRISPR/Cas gene therapy for inborn errors of immunity. Front. Immunol. 2023;14:1111777.

56. Xu W, Zhang S, Qin H, Yao K. From bench to bedside: cutting-edge applications of base editing and prime editing in precision medicine. J Transl Med. 2024;22:1133.

57. Kim H, Kim J. A guide to genome engineering with programmable nucleases. Nat Rev Genet. 2014;15:321-34.

58. Allen D, Kalter N, Rosenberg M, Hendel A. Homology-directed-repair-based genome editing in hspcs for the treatment of inborn errors of immunity and blood disorders. Pharmaceutics. 2023;15:1329.

59. Ferrari S, Vavassori V, Canarutto D, et al. Gene editing of hematopoietic stem cells: hopes and hurdles toward clinical translation. Front. Genome Ed. 2021;3:618378.

60. Sternberg SH, Redding S, Jinek M, Greene EC, Doudna JA. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature. 2014;507:62-7.

61. Hsu PD, Scott DA, Weinstein JA, et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol. 2013;31:827-32.

62. Dorset SR, Bak RO. The p53 challenge of hematopoietic stem cell gene editing. Mol Ther Methods Clin Dev. 2023;30:83-9.

63. Maganti HB, Bailey AJM, Kirkham AM, Shorr R, Pineault N, Allan DS. Persistence of CRISPR/Cas9 gene edited hematopoietic stem cells following transplantation: a systematic review and meta-analysis of preclinical studies. Stem Cells Transl Med. 2021;10:996-1007.

64. Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 2016;533:420-4.

65. Gaudelli NM, Komor AC, Rees HA, et al. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature. 2017;551:464-71.

66. Anzalone AV, Randolph PB, Davis JR, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576:149-57.

67. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable Dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337:816-21.

68. Humbert O, Radtke S, Samuelson C, et al. Therapeutically relevant engraftment of a CRISPR-Cas9-edited HSC-enriched population with HbF reactivation in nonhuman primates. Sci Transl Med. 2019;11:eaaw3768.

69. Zhang L, Li K, Liu Z, et al. Restoring T and B cell generation in X-linked severe combined immunodeficiency mice through hematopoietic stem cells adenine base editing. Mol Ther. 2024;32:1658-71.

70. Everette KA, Newby GA, Levine RM, et al. Ex vivo prime editing of patient haematopoietic stem cells rescues sickle-cell disease phenotypes after engraftment in mice. Nat. Biomed. Eng. 2023;7:616-28.

71. A Phase 1/2 study evaluating the safety and efficacy of a single dose of autologous CD34+ base edited hematopoietic stem cells (BEAM-101) in patients with sickle cell disease and severe vaso-occlusive crises (Beacon Trial). 2022. Available from: https://clinicaltrials.gov/study/NCT05456880 [Last accessed on 20 Mar 2026].

72. Heath JM, Stuart Orenstein J, Tedeschi JG, et al. Prime editing efficiently and precisely corrects causative mutation in chronic granulomatous disease, restoring myeloid function: toward development of a prime edited autologous hematopoietic stem cell therapy. Blood. 2023;142 Suppl:7129.

73. Schiroli G, Ferrari S, Conway A, et al. Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1. Sci Transl Med. 2017;9:eaan0820.

74. Pavel-dinu M, Wiebking V, Dejene BT, et al. Gene correction for SCID-X1 in long-term hematopoietic stem cells. Nat Commun. 2019;10:1634.

75. Brault J, Liu T, Liu S, et al. CRISPR-Cas9-AAV versus lentivector transduction for genome modification of X-linked severe combined immunodeficiency hematopoietic stem cells. Front. Immunol. 2023;13:1067417.

76. Castiello MC, Brandas C, Ferrari S, et al. Exonic knockout and knockin gene editing in hematopoietic stem and progenitor cells rescues RAG1 immunodeficiency. Sci Transl Med. 2024;16:eadh8162.

77. Iancu O, Allen D, Knop O, et al. Multiplex HDR for disease and correction modeling of SCID by CRISPR genome editing in human HSPCs. Mol Ther Nucleic Acids. 2023;31:105-21.

78. Allen D, Knop O, Itkowitz B, et al. CRISPR-Cas9 engineering of the RAG2 locus via complete coding sequence replacement for therapeutic applications. Nat Commun. 2023;14:6771.

79. Chang C, Lai Y, Westin E, et al. Modeling human severe combined immunodeficiency and correction by CRISPR/Cas9-enhanced gene targeting. Cell Reports. 2015;12:1668-77.

80. Roberts JL, Lengi A, Brown SM, et al. Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation. Blood. 2004;103:2009-18.

81. Rai R, Naseem A, Vetharoy W, et al. An improved medium formulation for efficient ex vivo gene editing, expansion and engraftment of hematopoietic stem and progenitor cells. Mol Ther Methods Clin Dev. 2023;29:58-69.

82. Lomova A, Clark DN, Campo-fernandez B, et al. Improving gene editing outcomes in human hematopoietic stem and progenitor cells by temporal control of DNA repair. Stem Cells. 2019;37:284-94.

83. De Ravin SS, Brault J, Meis RJ, et al. Enhanced homology-directed repair for highly efficient gene editing in hematopoietic stem/progenitor cells. Blood. 2021;137:2598-608.

84. Lattanzi A, Meneghini V, Pavani G, et al. Optimization of CRISPR/Cas9 delivery to human hematopoietic stem and progenitor cells for therapeutic genomic rearrangements. Mol Ther. 2019;27:137-50.

85. Cromer MK, Vaidyanathan S, Ryan DE, et al. Global transcriptional response to CRISPR/Cas9-AAV6-based genome editing in CD34+ hematopoietic stem and progenitor cells. Mol Ther. 2018;26:2431-42.

86. Gundry MC, Brunetti L, Lin A, et al. Highly efficient genome editing of murine and human hematopoietic progenitor cells by CRISPR/Cas9. Cell Reports. 2016;17:1453-61.

87. Aljanahi AA, Lazzarotto CR, Chen S, et al. Prediction and validation of hematopoietic stem and progenitor cell off-target editing in transplanted rhesus macaques. Mol Ther. 2022;30:209-22.

88. Lee B, Gin A, Wu C, et al. Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques. Cell Stem Cell. 2024;31:455-466.e4.

89. Kume A, Koremoto M, Mizukami H, et al. Selective growth advantage of wild-type lymphocytes in X-linked SCID recipients. Bone Marrow Transplant. 2002;30:113-8.

90. Newby GA, Yen JS, Woodard KJ, et al. Base editing of haematopoietic stem cells rescues sickle cell disease in mice. Nature. 2021;595:295-302.

91. Han W, Qiu H, Sun S, et al. Base editing of the HBG promoter induces potent fetal hemoglobin expression with no detectable off-target mutations in human HSCs. Cell Stem Cell. 2023;30:1624-1639.e8.

92. Liao J, Chen S, Hsiao S, et al. Therapeutic adenine base editing of human hematopoietic stem cells. Nat Commun. 2023;14:207.

93. Mcauley GE, Yiu G, Chang PC, et al. Human T cell generation is restored in CD3δ severe combined immunodeficiency through adenine base editing. Cell. 2023;186:1398-1416.e23.

94. Hoy SM. Exagamglogene autotemcel: first approval. Mol Diagn Ther. 2024;28:133-9.

Journal of Translational Genetics and Genomics
ISSN 2578-5281 (Online)
Follow Us

Portico

All published articles are preserved here permanently:

https://www.portico.org/publishers/oae/

Portico

All published articles are preserved here permanently:

https://www.portico.org/publishers/oae/