Romano Gaetano
Department of Biology, College of Science and Technology, Temple University, Bio-Life Science Building, Suite 456, 1900 N. 12th Street, Philadelphia, PA 19122, USA.
ISRN Oncol. 2012;2012:616310. doi: 10.5402/2012/616310. Epub 2012 Nov 22.
Integrating gene delivery systems allow for a more stable transgene expression in mammalian cells than the episomal ones. However, the integration of the shuttle vector within the cellular chromosomal DNA is associated with the risk of insertional mutagenesis, which, in turn, may cause malignant cell transformation. The use of a retroviral-derived vector system was responsible for the development of leukemia in five children, who participated in various clinical trials for the treatment of severe combined immunodeficiency (SCID-X1) in France and in the United Kingdom. Unfortunately, the hematological malignancy claimed the life of one patient in 2004, who was enrolled in the French clinical trial. In addition, adeno-associated-viral-(AAV-) mediated gene transfer induced tumors in animal models, whereas the Sleeping Beauty (SB) DNA transposon system was associated with insertional mutagenesis events in cell culture systems. On these grounds, it is necessary to develop safer gene delivery systems for the genetic manipulation of mammalian cells. This paper discusses the latest achievements that have been reported in the field of vector design.
与游离型基因传递系统相比，整合型基因传递系统能使哺乳动物细胞中的转基因表达更稳定。然而，穿梭载体整合到细胞染色体DNA中存在插入诱变的风险，进而可能导致恶性细胞转化。使用逆转录病毒衍生载体系统致使法国和英国参与重症联合免疫缺陷（SCID-X1）各种临床试验的五名儿童患白血病。不幸的是，2004年一名参加法国临床试验的患者因血液系统恶性肿瘤去世。此外，腺相关病毒（AAV）介导的基因转移在动物模型中诱发了肿瘤，而睡美人（SB）DNA转座子系统在细胞培养系统中与插入诱变事件有关。基于这些原因，有必要开发更安全的基因传递系统用于哺乳动物细胞的基因操作。本文讨论了载体设计领域已报道的最新成果。
