自身互补型腺相关病毒载体发展趋势

Trends in development of self-complementary adeno-associated virus vector

摘要:

重组腺相关病毒(Recombinant adeno-associated virus, rAAV)可以作为基因运载工具将目的基因运送入靶器官并对多种疾病发挥治疗作用。以rAAV为载体进行基因治疗的关键是病毒基因组由单链变为双链, 否则不能适时、有效表达目的基因。自身互补型rAAV(scrAAV)载体基因组本身以双链形式存在, 与常规的单链rAAV(ssrAAV)载体相比, 无论在表达时间还是表达强度上都有十分明显改善, 可显著降低在疾病治疗过程中由于载体本身所诱发的免疫反应。目前, scrAAV已经在肝脏疾病、中枢神经系统疾病、眼部疾病、干细胞修饰以及RNA干扰、核酶技术等领域得到应用。以下在介绍scrAAV载体构建、表达、定位的基础上, 以血友病B为主要对象, 阐述scrAAV的应用潜力及发展趋势。

Abstract:

Numerous studies and clinical trials have demonstrated the efficacy of recombinant adeno-associated virus gene delivery vectors. However, prior to expression, it is necessary to convert the single-stranded DNA genome into double-stranded DNA, which hinders the efficiency of these vectors. We can entirely circumvent this step through the use of self-complementary recombinant adeno-associated virus vector (scrAAV). ScrAAV packages an inverted repeat genome that can fold into double-stranded DNA without the requirement for DNA synthesis or base-pairing between multiple vector genomes. By using scrAAV, we could increase expression efficiency and reduce immune response caused by vectors themselves. Therefore, it is a promising vector for gene therapy. So far, it has been used in the treatment of hepatic diseases, central nervous system diseases, and eye diseases. It has also been used in the modifications of stem cells and as vectors for siRNA/miRNA and ribozymes. In this review, we focused on the preparation, expression and location of scrAAV both in vitro and in vivo. We mainly introduced the recent progress of scrAAV based therapy of Hemophilia B, in order to elucidate the potential and prospects of scrAAV in gene therapy.