Smith C
Division of Hematologic Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10021.
J Hematother. 1992 Summer;1(2):155-66. doi: 10.1089/scd.1.1992.1.155.
Gene therapy is a developing technology that may allow the treatment of a variety of congenital and acquired genetic disorders as well as infectious diseases through the introduction of exogenous genetic material into relevant cellular populations. Currently, the most effective method for gene transfer into cells of the hematopoietic system is with retroviral vectors. Appropriate cellular targets for gene transfer include totipotent hematopoietic stem cells as well as long-lived lineage committed cells such as T lymphocytes. Although retroviral vector-mediated gene transfer into totipotent stem cells and subsequent long-term expression of transduced genetic material in stem cell progeny has been observed in murine bone marrow transplantation experiments, similar observations have not been made in clinically relevant large-animal models. A number of recent advances in gene delivery systems, purification of stem cells, defining extramedullary sources of stem cells, characterizing the biologic processes that regulate the proliferation and developmental potential of stem cells, and construction of more effective models for assessing stem cells, may result in improvements in gene transfer into large animal and human totipotent stem cells.
基因治疗是一项正在发展的技术，它或许能够通过将外源遗传物质导入相关细胞群体来治疗多种先天性和后天性遗传疾病以及传染病。目前，将基因导入造血系统细胞的最有效方法是使用逆转录病毒载体。基因转移的合适细胞靶点包括全能造血干细胞以及如T淋巴细胞等长寿的定向谱系细胞。尽管在小鼠骨髓移植实验中已观察到逆转录病毒载体介导的基因转移到全能干细胞中以及转导的遗传物质在干细胞后代中的长期表达，但在临床相关的大型动物模型中尚未有类似的观察结果。基因递送系统、干细胞纯化、确定干细胞的髓外来源、表征调节干细胞增殖和发育潜能的生物学过程以及构建更有效的评估干细胞模型等方面的一些最新进展，可能会改善基因向大型动物和人类全能干细胞的转移。
