重症联合免疫缺陷的基因治疗：我们成功了吗？
Gene therapy for severe combined immunodeficiency: are we there yet?
作者信息
Cavazzana-Calvo Marina, Fischer Alain
机构信息
INSERM U768 and Université Paris Descartes, Paris, France.
出版信息
J Clin Invest. 2007 Jun;117(6):1456-65. doi: 10.1172/JCI30953.
Abstract
Inherited and acquired diseases of the hematopoietic system can be cured by allogeneic hematopoietic stem cell transplantation. This treatment strategy is highly successful when an HLA-matched sibling donor is available, but if not, few therapeutic options exist. Gene-modified, autologous bone marrow transplantation can circumvent the severe immunological complications that occur when a related HLA-mismatched donor is used and thus represents an attractive alternative. In this review, we summarize the advantages and limitations associated with the use of gene therapy to cure SCID. Insertional mutagenesis and technological improvements aimed at increasing the safety of this strategy are also discussed.
摘要
造血系统的遗传性和获得性疾病可通过异基因造血干细胞移植治愈。当有人类白细胞抗原（HLA）匹配的同胞供体时，这种治疗策略非常成功，但如果没有，则几乎没有治疗选择。基因修饰的自体骨髓移植可以规避使用相关HLA不匹配供体时出现的严重免疫并发症，因此是一种有吸引力的替代方法。在本综述中，我们总结了与使用基因疗法治疗重症联合免疫缺陷病（SCID）相关的优缺点。还讨论了插入诱变以及旨在提高该策略安全性的技术改进。
相似文献
1
Gene therapy for severe combined immunodeficiency: are we there yet?
J Clin Invest. 2007 Jun;117(6):1456-65. doi: 10.1172/JCI30953.
2
[Transplantation of genetically modified cells in the treatment of children with SCID: great hopes and recent disappointments].
Med Wieku Rozwoj. 2003 Jan-Mar;7(1):27-34.
3
Evolving Gene Therapy in Primary Immunodeficiency.
Mol Ther. 2017 May 3;25(5):1132-1141. doi: 10.1016/j.ymthe.2017.03.018. Epub 2017 Mar 31.
4
Gene therapy for adenosine deaminase deficiency.
Immunol Allergy Clin North Am. 2010 May;30(2):249-60. doi: 10.1016/j.iac.2010.02.003.
5
Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector.
Lancet. 2004;364(9452):2181-7. doi: 10.1016/S0140-6736(04)17590-9.
6
Advances in the treatment of Chronic Granulomatous Disease by gene therapy.
Curr Gene Ther. 2007 Jun;7(3):155-61. doi: 10.2174/156652307780859044.
7
Gene therapy for PIDs: progress, pitfalls and prospects.
Gene. 2013 Aug 10;525(2):174-81. doi: 10.1016/j.gene.2013.03.098. Epub 2013 Apr 6.
8
Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiency.
Curr Opin Allergy Clin Immunol. 2010 Dec;10(6):551-6. doi: 10.1097/ACI.0b013e32833fea85.
9
Hematopoietic stem cell gene therapy for adenosine deaminase-deficient severe combined immunodeficiency leads to long-term immunological recovery and metabolic correction.
Sci Transl Med. 2011 Aug 24;3(97):97ra80. doi: 10.1126/scitranslmed.3002716.
10
Gene therapy for SCID--a complication after remarkable progress.
Lancet. 2002 Oct 19;360(9341):1185-6. doi: 10.1016/S0140-6736(02)11290-6.
引用本文的文献
1
Translation of unspliced retroviral genomic RNA in the host cell is regulated in both space and time.
J Cell Biol. 2025 Apr 7;224(4). doi: 10.1083/jcb.202405075. Epub 2025 Jan 27.
2
Differentiation ability of hematopoietic stem cells and mesenchymal stem cells isolated from human peripheral blood.
Front Cell Dev Biol. 2024 Dec 18;12:1450543. doi: 10.3389/fcell.2024.1450543. eCollection 2024.
3
A Multifaceted Approach to Optimizing AAV Delivery to the Brain for the Treatment of Neurodegenerative Diseases.
Front Neurosci. 2021 Sep 24;15:747726. doi: 10.3389/fnins.2021.747726. eCollection 2021.
4
Successful Preclinical Development of Gene Therapy for Recombinase-Activating Gene-1-Deficient SCID.
Mol Ther Methods Clin Dev. 2020 Mar 31;17:666-682. doi: 10.1016/j.omtm.2020.03.016. eCollection 2020 Jun 12.
5
Darwinian selection within an individual or somatic selection: facts and models.
J Mol Cell Biol. 2019 Aug 19;11(8):719-722. doi: 10.1093/jmcb/mjz014.
6
ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome.
J Clin Immunol. 2018 May;38(4):484-493. doi: 10.1007/s10875-018-0496-9. Epub 2018 May 9.
7
Gene Therapy for Metabolic Diseases.
Transl Sci Rare Dis. 2016;1(1):73-89. doi: 10.3233/TRD-160007.
8
Advances in gene therapy for muscular dystrophies.
F1000Res. 2016 Aug 18;5. doi: 10.12688/f1000research.8735.1. eCollection 2016.
9
Towards in vivo amplification: Overcoming hurdles in the use of hematopoietic stem cells in transplantation and gene therapy.
World J Stem Cells. 2015 Dec 26;7(11):1233-50. doi: 10.4252/wjsc.v7.i11.1233.
10
[Heterogeneity of hematopoietic stem cell].
Zhonghua Xue Ye Xue Za Zhi. 2015 Oct;36(10):878-82. doi: 10.3760/cma.j.issn.0253-2727.2015.10.018.
本文引用的文献
1
Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy.
J Clin Invest. 2007 Aug;117(8):2225-32. doi: 10.1172/JCI31659.
2
Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006).
Clin Immunol. 2007 May;123(2):139-47. doi: 10.1016/j.clim.2006.12.009. Epub 2007 Feb 14.
3
Long-term T-cell reconstitution after hematopoietic stem-cell transplantation in primary T-cell-immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotype.
Blood. 2007 May 15;109(10):4575-81. doi: 10.1182/blood-2006-07-029090. Epub 2007 Feb 1.
4
Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells.
Nat Med. 2006 Dec;12(12):1397-402. doi: 10.1038/nm1504. Epub 2006 Nov 19.
5
Gene therapy of metachromatic leukodystrophy reverses neurological damage and deficits in mice.
J Clin Invest. 2006 Nov;116(11):3070-82. doi: 10.1172/JCI28873.
6
Gene therapy: X-SCID transgene leukaemogenicity.
Nature. 2006 Sep 21;443(7109):E5-6; discussion E6-7. doi: 10.1038/nature05219.
7
Insulators: exploiting transcriptional and epigenetic mechanisms.
Nat Rev Genet. 2006 Sep;7(9):703-13. doi: 10.1038/nrg1925. Epub 2006 Aug 15.
8
Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning.
Mol Ther. 2006 Oct;14(4):505-13. doi: 10.1016/j.ymthe.2006.06.007. Epub 2006 Aug 14.
9
Unique risk factors for insertional mutagenesis in a mouse model of XSCID gene therapy.
Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11730-5. doi: 10.1073/pnas.0603635103. Epub 2006 Jul 24.
10
Targeting lentiviral vectors to specific cell types in vivo.
Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11479-84. doi: 10.1073/pnas.0604993103. Epub 2006 Jul 24.
Zotero 插件