重组腺相关病毒包装容量研究进展

在以病毒载体介导的基因治疗研究中,重组腺相关病毒( rAAV)因其疗效和安全性方面的优势,是最有临床应用前景的载体.但其转基因包装容量一般不能超过5.0kb,给需要转导大片段基因的应用带来了困难,限制了rAAV在基因治疗研究中的应用.随着对rAAV细胞转导生物学过程研究的不断深入,发现了一些可以突破rAAV包装容量限制的技术,如反式剪接和同源重组策略,为拓展该载体应用范围提供了可能性.另外,rAAV包装容量限制的特点还可以被用来减少生产过程中具有可复制能力的类病毒杂质的污染,为rAAV的临床安全性提供了保障.

Package Capacity Limit of Recombinant Adeno-associated Virus Vector

Among viral vectors used in gene therapy approaches,recombinant adeno-associated virus(rAAV) vectors have shown great promise because of their efficacy and safety profiles.However,application of rAAV in gene therapy is limited by its packaging capacity of about 5.0 kb.Recently,due to a better understanding of the basic transduction biology of rAAV,several novel strategies have been developed to breakthrough the gene size limit of the small viral vector such as trans-splicing and homologous recombination techniques.The package limit property of rAAV can also be used to reduce the contamination of the replication-competent AAV in large scaled production process in order to meet the safety requirement of clinic trials.