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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >EFFICIENT GENE TRANSFER INTO HUMAN HEPATOCYTES BY BACULOVIRUS VECTORS
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EFFICIENT GENE TRANSFER INTO HUMAN HEPATOCYTES BY BACULOVIRUS VECTORS

机译:杆状病毒载体将基因有效地转移到人肝细胞中

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摘要

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. [References: 46]
机译:病毒载体是最有效的基因传递工具,寻找组织特异性感染病毒对于体内基因治疗策略的发展很重要。杆状病毒加利福尼亚苜蓿核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,并且其宿主特异性被认为仅限于节肢动物。在这里,我们证明了重组人加州农杆菌核多角体病毒被人肝细胞通过内体途径有效地吸收了。体外在人和兔肝细胞中观察到了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要低得多。杆状病毒进行基因转移的效率大大超过了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将其用作用于肝定向基因转移的载体,但是突出了在处理某些重组杆状病毒中的潜在风险。 [参考:46]

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