Hofmann C, Sandig V, Jennings G, Rudolph M, Schlag P, Strauss M
Max-Planck-Gesellschaft, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10099-103. doi: 10.1073/pnas.92.22.10099.
Viral vectors are the most efficient tools for gene delivery, and the search for tissue-specific infecting viruses is important for the development of in vivo gene therapy strategies. The baculovirus Autographa californica nuclear polyhedrosis virus is widely used as a vector for expression of foreign genes in insect cells, and its host specificity is supposed to be restricted to arthropods. Here we demonstrate that recombinant A. californica nuclear polyhedrosis virus is efficiently taken up by human hepatocytes via an endosomal pathway. High-level reporter gene expression from heterologous promoters was observed in human and rabbit hepatocytes in vitro. Mouse hepatocytes and some other epithelial cell types are targeted at a considerably lower rate. The efficiency of gene transfer by baculovirus considerably exceeds that obtained by calcium phosphate or lipid transfection. These properties of baculovirus suggest a use for it as a vector for liver-directed gene transfer but highlight a potential risk in handling certain recombinant baculoviruses.
病毒载体是基因传递最有效的工具，寻找组织特异性感染病毒对于体内基因治疗策略的发展至关重要。杆状病毒苜蓿银纹夜蛾核型多角体病毒被广泛用作在昆虫细胞中表达外源基因的载体，其宿主特异性被认为仅限于节肢动物。在此我们证明，重组苜蓿银纹夜蛾核型多角体病毒可通过内吞途径被人肝细胞有效摄取。在体外的人肝细胞和兔肝细胞中观察到来自异源启动子的高水平报告基因表达。小鼠肝细胞和其他一些上皮细胞类型的靶向率则低得多。杆状病毒的基因转移效率大大超过磷酸钙或脂质转染所获得的效率。杆状病毒的这些特性表明它可作为肝脏定向基因转移的载体，但也凸显了处理某些重组杆状病毒时的潜在风险。
