In vitro and in vivo gene delivery by recombinant baculoviruses
In vitro and in vivo gene delivery by recombinant baculoviruses
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DOI：
10.1128/jvi.77.18.9799-9808.2003
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发表时间：
2003-09-01
影响因子：
5.4
通讯作者：
Matsuura, Y
中科院分区：
文献类型：
--
作者：
Tani, H;Limn, CK;Matsuura, Y
虽然重组杆状病毒载体可以在体外有效地将基因转移到哺乳动物细胞中，但由于血清补体对杆状病毒的灭活作用，体内的基因转移一直受到阻碍。在病毒粒子表面含有过量包膜蛋白gp64或其他病毒包膜蛋白的重组杆状病毒比未经修饰的杆状病毒更有效地将外源基因送入各种哺乳动物细胞系。在这项研究中，我们检测了含有水疱性口炎病毒(VSVG)或狂犬病病毒包膜蛋白的重组杆状病毒在体外和体内的基因转移效率。这些重组病毒在体外将报告基因有效地转移到神经细胞系、原代大鼠神经细胞和原代小鼠骨细胞中。VSVG修饰的杆状病毒比未修饰的杆状病毒对动物血清灭活表现出更强的抵抗力。补体激活途径的合成抑制剂绕过了未经修饰的杆状病毒的血清灭活。此外，VSVG修饰的杆状病毒可以通过体内直接接种将报告基因转导到小鼠的大脑皮层和睾丸。这些结果表明，重组杆状病毒载体与补体抑制剂联合应用于体内基因治疗是可能的。
Although recombinant baculovirus vectors can be an efficient tool for gene transfer into mammalian cells in vitro, gene transduction in vivo has been hampered by the inactivation of baculoviruses by serum complement. Recombinant baculoviruses possessing excess envelope protein gp64 or other viral envelope proteins on the virion surface deliver foreign genes into a variety of mammalian cell lines more efficiently than the unmodified baculovirus. In this study, we examined the efficiency of gene transfer both in vitro and in vivo by recombinant baculoviruses possessing envelope proteins derived from either vesicular stomatitis virus (VSVG) or rabies virus. These recombinant viruses efficiently transferred reporter genes into neural cell lines, primary rat neural cells, and primary mouse osteal cells in vitro. The VSVG-modified bacullovirus exhibited greater resistance to inactivation by animal sera than the unmodified baculovirus. A synthetic inhibitor of the complement activation pathway circumvented the serum inactivation of the unmodified baculovirus. Furthermore, the VSVG-modified baculovirus could transduce a reporter gene into the cerebral cortex and testis of mice by direct inoculation in vivo. These results suggest the possible use of the recombinant bacullovirus vectors in combination with the administration of complement inhibitors for in vivo gene therapy.