Kremer Eric J
Institut de Génétique Moléculaire de Montpellier CNRS UMR 5535, 1919 Route de Mende, 34293 Montpellier, France.
J Gene Med. 2004 Feb;6 Suppl 1:S139-51. doi: 10.1002/jgm.497.
This review deals primarily with canine adenovirus serotype 2 (CAV-2) vectors and gives a simplified overview of how the various domains of virology, cellular and molecular biology, as well as immunology, come into play when trying to understand and ameliorate adenovirus (Ad)-mediated gene transfer. The generation of early region 1 (E1)-deleted (DeltaE1) CAV-2 vectors, the lack of pre-existing humoral immunity, trafficking, the use of the coxsackie B adenovirus receptor (CAR), the surprising neuronal tropism, and the ability to migrate via axons to afferent regions of the central and peripheral nervous system, are described. Due to these intrinsic properties, CAV-2 vectors may be powerful tools for the study of the pathophysiology and potential treatment of neurodegenerative diseases like lysosomal storage disorders, Parkinson's, Alzheimer's, Huntington's, amyotrophic lateral sclerosis, and others. Other potential uses include anti-tumoral and anti-viral vaccines, tracer of synaptic junctions, pain therapy, cancer therapy (e.g. K9 CRAds), and gene transfer to other somatic tissues.
本综述主要涉及犬腺病毒2型(CAV - 2)载体,并简要概述了在试图理解和改善腺病毒(Ad)介导的基因转移时,病毒学、细胞与分子生物学以及免疫学的各个领域是如何发挥作用的。文中描述了缺失早期区域1(E1)的(ΔE1)CAV - 2载体的产生、不存在预先存在的体液免疫、运输、柯萨奇B腺病毒受体(CAR)的使用、令人惊讶的神经嗜性以及通过轴突迁移至中枢和外周神经系统传入区域的能力。由于这些内在特性,CAV - 2载体可能是研究溶酶体贮积症、帕金森病、阿尔茨海默病、亨廷顿病、肌萎缩侧索硬化症等神经退行性疾病的病理生理学及潜在治疗方法的有力工具。其他潜在用途包括抗肿瘤和抗病毒疫苗、突触连接示踪剂、疼痛治疗、癌症治疗(如K9 CRAds)以及向其他体细胞组织的基因转移。