Integrase Defective, Nonintegrating Lentiviral Vectors
Integrase Defective, Nonintegrating Lentiviral Vectors
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DOI：
10.1007/978-1-60761-533-0_6
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Cara, Andrea
中科院分区：
文献类型：
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作者：
Michelini, Zuleika;Negri, Donatella;Cara, Andrea
慢病毒载体是一种强有力的工具，基因转移到靶细胞在体外和体内。然而，由于病毒感染后的插入诱变，存在关于其在基因转移方案中使用的安全性的担忧。一旦在靶细胞中，并且除了整合的前病毒DNA之外，慢病毒载体产生附加型形式的DNA（E-DNA），其具有转录活性。因此，一种提高安全性的策略将设想阻断慢病毒载体的整合，同时允许产生E-DNA。这种非整合慢病毒载体可以通过在亲本包装载体的整合酶（IN）蛋白中引入突变来产生。这些载体从根本上不同于亲本IN感受态对应物，因此为这类慢病毒载体开辟了新的途径，其是用于基因治疗策略、疫苗接种方案的新基因递送系统，并作为抗整合酶药物发现的工具。
Lentiviral vectors are a powerful tool for gene transfer into target cells in vitro and in vivo. However, there are concerns about safety with regard to their use in gene transfer protocols because of insertional mutagenesis following viral infection. Once in the target cells, and in addition to the integrated proviral DNA, lentiviral vectors produce episomal forms of DNA (E-DNA), which are transcriptionally active. Therefore, one strategy to improve safety would envision the block integration of the lentiviral vector while allowing production of E-DNA. Such nonintegrating lentiviral vectors can be produced by introducing mutations in the Integrase (IN) protein of the parental packaging vector. These vectors are fundamentally different from the parental IN competent counterpart, thus opening new avenues for this class of lentiviral vectors its a new gene delivery system for gene therapy strategies, vaccination protocols and as a tool for anti-Integrase drug discovery.