重组腺相关病毒载体相关性杂质

Recombinant adeno-associated virus vector related impurities

摘要:

可以稳定表达治疗基因而无明显不良反应的重组腺相关病毒 (rAAV) 载体被认为是最有发展前景的基因治疗载体。但如何建立可以有效去除rAAV载体内具有潜在致病危害的杂质、产品质量符合临床使用要求的纯化工艺是研究人员面临的巨大挑战。其中针对载体相关性杂质的纯化工艺尤为关键，因为该类杂质的性质与真正的rAAV载体极其相似，一旦存在便难以去除，且会引起严重不良反应。以下总结了该类杂质形成的过程及有别于rAAV载体的特点，并对可以防止其生成或将其与rAAV载体有效分离的技术手段进行了评价。

Abstract:

Recombinant adeno-associated virus (rAAV)-based vectors that can stably express therapeutic genes in vivo without detectable side-effect have shown great promise for human gene therapy. A major challenge for translation of promising research to clinical development is how to establish clinically compatible purification methods in separating rAAV from potentially pathogenic impurities, especially rAAV vector-related impurities, a class of impurities corresponding to AAV particles that closely resemble bona fide vectors and are difficult to remove. In this review we summarize the assembly process of rAAV vector-related impurities and their characteristics differed with rAAV vectors, and evaluate several current technologies to prevent their formation or separate them from rAAV stocks.