Integrating gene delivery systems allow for a more stable transgene expression in mammalian cells than the episomal ones.\r\nHowever, the integration of the shuttle vector within the cellular chromosomal DNA is associated with the risk of insertional\r\nmutagenesis, which, in turn, may cause malignant cell transformation. The use of a retroviral-derived vector system was\r\nresponsible for the development of leukemia in five children, who participated in various clinical trials for the treatment of severe\r\ncombined immunodeficiency (SCID-X1) in France and in the United Kingdom. Unfortunately, the hematological malignancy\r\nclaimed the life of one patient in 2004, who was enrolled in the French clinical trial. In addition, adeno-associated-viral-(AAV-)\r\nmediated gene transfer induced tumors in animal models, whereas the Sleeping Beauty (SB) DNA transposon system was\r\nassociated with insertional mutagenesis events in cell culture systems. On these grounds, it is necessary to develop safer gene\r\ndelivery systems for the genetic manipulation of mammalian cells. This paper discusses the latest achievements that have been\r\nreported in the field of vector design.
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