Roelvink P W, Mi Lee G, Einfeld D A, Kovesdi I, Wickham T J
Research and Development, GenVec Inc., 65 West Watkins Mill Road, Gaithersburg, MD 20879, USA.
Science. 1999 Nov 19;286(5444):1568-71. doi: 10.1126/science.286.5444.1568.
The human adenovirus serotype 5 (Ad5) is used widely for applications in human gene therapy. Cellular attachment of Ad5 is mediated by binding of the carboxyl-terminal knob of its fiber coat protein to the Coxsackie adenovirus receptor (CAR) protein. However, Ad5 binding to CAR hampers the development of adenovirus vectors capable of specifically targeting (diseased) tissues or organs. Through sequence analysis and mutagenesis, a conserved receptor-binding region was identified on the side of three divergent CAR-binding knobs. The feasibility of simultaneous CAR ablation and redirection of an adenovirus to a new receptor is demonstrated.
人5型腺病毒（Ad5）广泛应用于人类基因治疗。Ad5的细胞附着是通过其纤维衣壳蛋白的羧基末端球形结构域与柯萨奇腺病毒受体（CAR）蛋白结合介导的。然而，Ad5与CAR的结合阻碍了能够特异性靶向（患病）组织或器官的腺病毒载体的开发。通过序列分析和诱变，在三个不同的CAR结合球形结构域一侧鉴定出一个保守的受体结合区域。证明了同时消除CAR并将腺病毒重定向至新受体的可行性。
