Bilbao G, Feng M, Rancourt C, Jackson W H, Curiel D T
Gene Therapy Program, Comprehensive Cancer Center, University of Alabama at Birmingham, 35294-3300, USA.
FASEB J. 1997 Jul;11(8):624-34. doi: 10.1096/fasebj.11.8.9240964.
Gene therapy to correct defective genes requires efficient gene delivery and long-term gene expression. Realization of both goals with available vector systems has so far not been achieved. As a novel approach to solve this problem, we have developed a chimeric viral vector system that exploits favorable aspects of both adenoviral and retroviral vectors. In this schema, adenoviral vectors induce target cells to function as transient retroviral producer cells in vivo. The progeny retroviral vector particles can then effectively achieve stable transduction of neighboring cells. In this system, the nonintegrative adenoviral vector is rendered functionally integrative via the intermediate generation of an induced retroviral producer cell. Such chimeric vectors may now allow realization of the requisite goals for specific gene therapy applications.
纠正缺陷基因的基因治疗需要高效的基因传递和长期的基因表达。目前利用现有的载体系统尚未实现这两个目标。作为解决这一问题的新方法，我们开发了一种嵌合病毒载体系统，该系统利用了腺病毒载体和逆转录病毒载体的有利方面。在此方案中，腺病毒载体诱导靶细胞在体内充当瞬时逆转录病毒产生细胞。子代逆转录病毒载体颗粒随后可有效实现对邻近细胞的稳定转导。在该系统中，非整合型腺病毒载体通过诱导产生的逆转录病毒产生细胞的中间生成而在功能上变为整合型。这种嵌合载体现在可能使特定基因治疗应用所需的目标得以实现。
