Gene transfer therapy for heritable disease: cell and expression targeting.
Gene transfer therapy for heritable disease: cell and expression targeting.
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遗传性疾病的基因转移疗法：细胞和表达靶向。
DOI：
10.1098/rstb.1993.0019
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Caskey,CT
中科院分区：
文献类型：
--
作者：
Mitani,K;Clemens,PR;Moseley,AB;Caskey,CT
基因治疗被定义为递送功能基因以在体细胞组织中表达，目的是治愈疾病。可能需要不同的基因转移策略来靶向不同的组织。腺苷脱氨酶（ADA）缺乏症是一个很好的基因治疗模型，靶向一个罕见的多能造血干细胞群体能够自我更新。我们提出的证据，高效的基因转移和持续表达的人类ADA在人类原始造血祖细胞使用逆转录病毒上清液与支持性基质层。也成功地转导了干细胞富集（CD34+）部分。Duchenne型肌营养不良症（DMD）也是体细胞基因治疗的良好模型。该模型提出的两个挑战是基因的大尺寸和大量的靶细胞。已在转基因mdx小鼠中使用全长和截短形式的肌营养不良蛋白cDNA证明了种系基因转移和表型校正。我们在这里提出了一个删除诱变策略，截断肌营养不良蛋白的cDNA，使它可以容纳逆转录病毒和腺病毒载体体细胞基因治疗有用。
Gene therapy is defined as the delivery of a functional gene for expression in somatic tissues with the intent to cure a disease. Different gene transfer strategies may be required to target different tissues. Adenosine deaminase (ADA) deficiency is a good gene therapy model for targeting a rare population of pluripotent hematopoietic stem cells capable of self-renewal. We present evidence for the highly efficient gene transfer and sustained expression of hum an ADA in human primitive hematopoietic progenitors using retroviral supernatant with a supportive stromal layer. A stem cell-enriched (CD34+) fraction was also successfully transduced. Duchenne muscular dystrophy (DMD) is also a good model for somatic gene therapy. Two of the challenges presented by this model are the large size of the gene and the large number of target cells. Germline gene transfer and correction of the phenotype has been demonstrated in transgenicmdxmice using both a full-length and a truncated form of the dystrophin cDNA. We present here a deletion mutagenesis strategy to truncate the dystrophin cDNA such that it can be accommodated by retroviral and adenoviral vectors useful for somatic gene therapy.