Feng M, Jackson W H, Goldman C K, Rancourt C, Wang M, Dusing S K, Siegal G, Curiel D T
Department of Pathology, University of Alabama at Birmingham 35294, USA.
Nat Biotechnol. 1997 Sep;15(9):866-70. doi: 10.1038/nbt0997-866.
Gene therapy to correct defective genes requires efficient gene delivery and long-term gene expression. The available vector systems have not allowed the simultaneous achievement of both goals. We have developed a chimeric viral vector system that incorporates favorable aspects of both adenoviral and retroviral vectors. Adenoviral vectors induce target cells to function as transient retroviral producer cells in vivo. The progeny retroviral vector particles are then able to stably transduce neighboring cells. In this system, the nonintegrative adenoviral vector is rendered functionally integrative via the intermediate generation of a retroviral producer cell. The chimeric vectors may allow realization of the requisite goals for specific gene-therapy applications.
纠正缺陷基因的基因疗法需要高效的基因传递和长期的基因表达。现有的载体系统无法同时实现这两个目标。我们开发了一种嵌合病毒载体系统,该系统融合了腺病毒载体和逆转录病毒载体的有利方面。腺病毒载体可诱导靶细胞在体内充当瞬时逆转录病毒生产细胞。然后,子代逆转录病毒载体颗粒能够稳定地转导相邻细胞。在该系统中,非整合型腺病毒载体通过逆转录病毒生产细胞的中间生成而在功能上变为整合型。这种嵌合载体可能会实现特定基因治疗应用所需的目标。