腺苷脱氨酶缺乏症的基因治疗。

Gene therapy for adenosine deaminase deficiency.

作者信息

Parkman R, Weinberg K, Crooks G, Nolta J, Kapoor N, Kohn D

机构信息

Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, California, USA.

出版信息

Annu Rev Med. 2000;51:33-47. doi: 10.1146/annurev.med.51.1.33.

DOI:10.1146/annurev.med.51.1.33

PMID:10774451

Abstract

The clinical gene therapy trials for adenosine deaminase (ADA) deficiency have defined both the potential benefits and the present limitations of gene therapy with hematopoietic stem cells (HSC). Current clinical results indicate that (a) both umbilical cord blood and neonatal bone marrow HSC can be transduced with murine retroviral-based vectors, (b) the transduced HSC can engraft in nonmyeloablated patients, (c) the frequency of HSC transduction/engraftment is low (1/10,000), (d) an in vivo selective advantage can exist for transduced T lymphoid progeny, and (e) the transduced ADA gene is not expressed in nondividing T lymphocytes. Improving the clinical results of gene therapy for ADA deficiency and other genetic diseases involving HSC will require (a) developing new vectors that express the transduced gene in nondividing cells and (b) increasing the frequency of stable HSC transduction.

摘要

针对腺苷脱氨酶（ADA）缺乏症的临床基因治疗试验明确了造血干细胞（HSC）基因治疗的潜在益处和当前局限性。目前的临床结果表明：（a）脐带血和新生儿骨髓造血干细胞均可被基于鼠逆转录病毒的载体转导；（b）转导后的造血干细胞可植入未进行清髓处理的患者体内；（c）造血干细胞转导/植入的频率较低（1/10,000）；（d）转导后的T淋巴细胞后代可能存在体内选择性优势；（e）转导后的ADA基因在不分裂的T淋巴细胞中不表达。要改善ADA缺乏症及其他涉及造血干细胞的遗传疾病的基因治疗临床结果，需要：（a）开发能在不分裂细胞中表达转导基因的新型载体；（b）提高稳定的造血干细胞转导频率。