Neschadim Anton, McCart J Andrea, Keating Armand, Medin Jeffrey A
Division of Stem Cell and Developmental Biology, Ontario Cancer Institute, Toronto, Ontario, Canada.
Biol Blood Marrow Transplant. 2007 Dec;13(12):1407-16. doi: 10.1016/j.bbmt.2007.09.014.
Hematopoietic stem cells comprise a prominent target for gene therapy aimed at treating various genetic and acquired disorders. A number of limitations associated with hematopoietic cell transplantation can be circumvented by the use of cells stably modified by retroviral gene transfer. Oncoretroviral and lentiviral vectors offer means for generating efficient and stable transgene expression. This review summarizes the state of the field today in terms of vector development and clinical experimentation. In particular, concerns with the safety of retroviral vectors intended for clinical gene transfer, applicability of preclinical data in directing clinical trial design, and recent research aimed at resolving some of these issues are addressed. Finally, this review underlines the specific advantages offered by lentiviral gene-transfer vectors for gene therapy in stem cells.
造血干细胞是旨在治疗各种遗传性和后天性疾病的基因治疗的一个重要靶点。通过使用经逆转录病毒基因转移稳定修饰的细胞，可以规避与造血细胞移植相关的一些限制。γ-逆转录病毒载体和慢病毒载体为产生高效且稳定的转基因表达提供了手段。本综述总结了目前该领域在载体开发和临床试验方面的进展。特别讨论了用于临床基因转移的逆转录病毒载体的安全性问题、临床前数据在指导临床试验设计中的适用性，以及近期旨在解决其中一些问题的研究。最后，本综述强调了慢病毒基因转移载体在干细胞基因治疗中所具有的特定优势。
