腺相关病毒基因治疗载体的改良与应用

腺相关病毒(adeno-associated virus,AAV)的非致病特性使得以其为基础的重组病毒载体具有卓越的安全性,成为在基因治疗中最富吸引力的候选载体之一,并且在多种疾病的临床治疗中广泛应用。在过去的十余年中,随着分子病毒学领域对AAV基础研究的进展,研究者不断地为重组腺相关病毒的生产和改良提供新的思路和方案,以改善其对宿主或靶向细胞的感染选择性和转导效率,其中相当部分已逐渐向临床试验阶段过渡。本综述将在介绍AAV基本生物学特征的同时,结合一些实验室研究的成功案例,重点讨论AAV的改良策略、实施方案与应用特点,并对当前以AAV为载体的基因治疗的全球现状及其所面临的挑战与前景进行分析和探讨。

Improvements and Applications of Adeno-associated Virus Vectors for Gene Therapy

The non-pathogenic property of adeno-associated virus(AAV)has made its recombinants one of the most attractive candidate gene therapy vectors for its outstanding feature in safety, which have already been applied in the clinics for the treatments of a variety of diseases. As the basic researches in molecular virology of AAV have progressed rapidly within the past two decades, novel strategies to improve the specificity of AAV infection in host/targeted cells and the efficiency of viral transduction have been attempted, part of which are being subsequently translated for clinical trials. This review will introduce the current understandings of AAV with its basic biological characteristics, and take several successful laboratory researches as examples to discuss the strategies and approaches for developing improved AAV vectors as well as their features for application. The current status and the challenges for AAV-mediated gene therapy are also addressed.