Noureddini Sam C, Curiel David T
VectorLogics, Inc., 550 11th Street South, Birmingham, Alabama 35294, USA.
Mol Pharm. 2005 Sep-Oct;2(5):341-7. doi: 10.1021/mp050045c.
Adenovirus serotype 5 (Ad5) continues to be regarded as a gene delivery vehicle of high utility for a variety of clinical applications. However, targeting of the virus to alternate, non-native receptors has become a mandate for many gene therapy approaches, as inefficient viral transduction of target tissues has proven detrimental to the utility of Ad5. Thus, various targeting strategies have been endeavored to the end of highly specific cellular transduction, including that of genetic manipulation of the viral capsid. Modification of the tropism-determining fiber protein and other capsid locales has allowed vectorologists to develop vectors that are highly superior to the first-generation adenoviruses employed for gene therapy. Herein, the various genetic targeting strategies for Ad5 are reviewed, and the various schemas in which targeted transduction has been achieved with tropism-modified vectors are outlined.
5型腺病毒(Ad5)仍然被认为是一种在多种临床应用中具有高度实用性的基因传递载体。然而,将病毒靶向至替代的、非天然受体已成为许多基因治疗方法的一项要求,因为已证明目标组织中低效的病毒转导对Ad5的实用性有害。因此,为了实现高度特异性的细胞转导,人们尝试了各种靶向策略,包括对病毒衣壳进行基因操作。对决定嗜性的纤维蛋白和其他衣壳区域的修饰使载体学家能够开发出比用于基因治疗的第一代腺病毒优越得多的载体。本文综述了Ad5的各种基因靶向策略,并概述了利用嗜性修饰载体实现靶向转导的各种方案。