Van Tendeloo V F, Van Broeckhoven C, Berneman Z N
Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Belgium.
Leukemia. 2001 Apr;15(4):523-44. doi: 10.1038/sj.leu.2402085.
Ever since the development of technology allowing the transfer of new genes into eukaryotic cells, the hematopoietic system has been an obvious and desirable target for gene therapy. The last 10 years have witnessed an explosion of interest in this approach to treat human disease, both inherited and acquired, with the initiation of multiple clinical protocols. All gene therapy strategies have two essential technical requirements. These are: (1) the efficient introduction of the relevant genetic material into the target cell and (2) the expression of the transgene at therapeutic levels. Conceptual and technical hurdles involved with these requirements are still the objects of active research. To date, the most widely used and best understood vectors for gene transfer in hematopoietic cells are derived from retroviruses, although they suffer from several limitations. However, as gene transfer mechanisms become more efficient and long-term gene expression is enhanced, the variety of diseases that can be tackled by gene therapy will continue to expand. However, until the problem of delivery and subsequent expression is adequately resolved, gene therapy will not realize its full potential. The first part of this review gives an overview of the gene delivery technology available at present to transfer genetic sequences in human somatic cells. The relevance of the hematopoietic system to the development of gene therapy strategies as well as hematopoietic cell-based gene therapy is discussed in the second part.
自从能够将新基因导入真核细胞的技术发展以来，造血系统一直是基因治疗的一个明显且理想的靶点。在过去十年中，随着多个临床方案的启动，人们对这种治疗人类遗传性和后天性疾病的方法的兴趣激增。所有基因治疗策略都有两个基本技术要求。它们是：（1）将相关遗传物质有效导入靶细胞；（2）转基因在治疗水平上表达。与这些要求相关的概念和技术障碍仍是积极研究的对象。迄今为止，造血细胞中最广泛使用且理解最透彻的基因转移载体源自逆转录病毒，尽管它们存在一些局限性。然而，随着基因转移机制变得更加高效且长期基因表达得到增强，基因治疗能够解决的疾病种类将持续扩大。然而，在递送和后续表达问题得到充分解决之前，基因治疗无法充分发挥其潜力。本综述的第一部分概述了目前可用于在人类体细胞中转移基因序列的基因递送技术。第二部分讨论了造血系统与基因治疗策略发展以及基于造血细胞的基因治疗的相关性。
