昆虫杆状病毒应用于哺乳动物基因治疗的研究进展

A novel application of baculovirus in mammalian gene therapy

杆状病毒是一类宿主特异性的昆虫病毒。昆虫杆状病毒表达系统是一个高效的真核表达系统,被广泛用于在昆虫细胞或昆虫幼虫中生产外源蛋白质。杆状病毒不能感染哺乳动物,却可以进入不同物种和组织来源的多种哺乳动物细胞,并在合适的哺乳动物启动子控制下表达外源基因。杆状病毒在哺乳动物细胞中不能复制,对细胞没有毒性,加上杆状病毒本身具有基因组大、可操作性好等优点,作为哺乳动物基因治疗的载体,将治疗基因传递给哺乳动物细胞已受到了广泛关注。在此就杆状病毒作为基因治疗载体的最新研究进展进行了阐述并探讨其发展趋势。

Baculovirus has been widely used for the production of recombinant proteins in insect cells. The extremely high yield by baculovirus-infected insect cells or larvae makes it an attractive tool for pharmaceutical protein production. Since the finding that baculovirus can efficiently transduce mammalian cells, the applications of baculovirus have been greatly expanded, Although AcMNPV （Autographa californica multiple NPV） fails to replicate in vertebrate cells, it does express alien genes with levels of expression that are dependent on the strength of the promoter used to drive transcription of the foreign gene. Following these findings, subsequent studies have rapidly expanded the list of permissive cells that include cell lines originating from human, rodent, porcine, bovine and even fish sources. Many tries have been done to study the mechanism of baxulovirus entry into mammalian cells, but the events responsible for virus uptake and detailed mechanisms of intracellular movement and nuclear entry of the virus are still largely unknown. The application of modified baculoviruses for in vivo gene delivery has also been demonstrated, In contrast to other commonly used viral vectors, baculoviruses have the unique property of being incapable of initiating a replication cycle and producing infectious virus in mammalian cells. The AcMNPV genome is large, thus rendering the virus flexibility to carry multiple genes or large inserts. The recombinant viruses can be readily constructed and produced to high titers simply by infecting insect cells, initiate little to none microscopically observable cytopathic effects on mammalian cells and have a good biosafety profile, These attributes will undoubtedly lead to the increased application and continued development of this system for efficient gene delivery into mammalian cells.