Mizuguchi Hiroyuki, Hayakawa Takao
Project III, National Institute of Health Sciences, Osaka Branch, Fundamental Research Laboratories for Development of Medicine, Osaka 567-0085, Japan.
Hum Gene Ther. 2004 Nov;15(11):1034-44. doi: 10.1089/hum.2004.15.1034.
Recombinant adenovirus (Ad) vectors continue to be the preferred vectors for gene therapy and the study of gene function because they are relatively easy to construct, can be produced at high titer, and have high transduction efficiency. However, in some applications gene transfer with Ad vectors is less efficient because the target cells lack expression of the primary receptor, coxsackievirus and adenovirus receptor (CAR). Another problem is the wide biodistribution of vector in tissue following in vivo gene transfer because of the relatively broad tissue expression of CAR. To overcome these limitations, various approaches have been developed to modify Ad tropism. In one approach, the capsid proteins of Ad are modified, such as with the addition of foreign ligands or the substitution of the fiber with other types of Ad fiber, in combination with the ablation of native tropism. In other approaches, Ad vectors are conjugated with adaptor molecules, such as antibody and fusion protein containing an anti-Ad single-chain antibody (scFv) or the extracellular domain of CAR with the targeting ligands, or chemically modified with polymers containing the targeting ligands. In this paper, we review advances in the development of targeted Ad vectors.
重组腺病毒（Ad）载体仍然是基因治疗和基因功能研究的首选载体，因为它们相对易于构建、可以高滴度生产且具有高转导效率。然而，在某些应用中，由于靶细胞缺乏主要受体柯萨奇病毒和腺病毒受体（CAR）的表达，Ad载体的基因转移效率较低。另一个问题是，由于CAR在组织中的表达相对广泛，体内基因转移后载体在组织中的生物分布较广。为了克服这些限制，人们开发了各种方法来改变Ad的嗜性。一种方法是修饰Ad的衣壳蛋白，例如添加外源配体或用其他类型的Ad纤维替代纤维，并消除天然嗜性。在其他方法中，Ad载体与衔接分子偶联，例如抗体和含有抗Ad单链抗体（scFv）或CAR胞外结构域与靶向配体的融合蛋白，或用含有靶向配体的聚合物进行化学修饰。在本文中，我们综述了靶向Ad载体开发的进展。
