Adenoviral preterminal protein stabilizes mini-adenoviral genomes in vitro and in vivo.

Adenoviral preterminal protein stabilizes mini-adenoviral genomes in vitro and in vivo.
复制标题

腺病毒前终端蛋白可在体外和体内稳定微型腺病毒基因组。

DOI:
10.1038/nbt1297-1383
复制
发表时间:
1997
影响因子:
46.9
通讯作者:
Kay,MA
Kay,MA
中科院分区:
工程技术1区
文献类型:
--
作者:
Lieber,A;He,CY;Kay,MA

文献摘要

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在没有宿主免疫的情况下,非整合的第一代腺病毒载体在小鼠静止转导细胞的细胞核中保持稳定。缺失病毒E1、E2、E3和晚期基因,但含有病毒反向末端重复序列(ITR)、转基因表达盒(人α1-抗胰蛋白酶)和病毒E4基因的小型腺病毒基因组(9 kb)在体外或体内转导细胞方面与第一代E1缺失载体同样有效。与第一代载体相反,基因表达以及载体DNA在用缺失的腺病毒基因组转导的细胞中是短暂的。我们证明,腺病毒E2-preterminal蛋白从载体或反式共表达稳定的微型基因组在体外和体内没有细胞毒性的证据。
In the absence of host immunity, nonintegrating, first-generation adenoviral vectors remain stable in the nucleus of quiescent transduced cells in mice. A mini-adenoviral genome (9 kb) deleted for viral E1, E2, E3, and late genes, but containing the viral inverted terminal repeats (ITRs), transgene expression cassette (human α1-antitrypsin), and the viral E4 genes was equally efficient at transducing cells in vitro or in vivo as first generation, E1-deleted vectors. In contrast to a first generation vector, gene expression as well as vector DNA was short-lived in cells transduced with the deleted adenoviral genome. We demonstrate that coexpression of the adenoviral E2-preterminal protein from the vector or in trans stabilizes the mini-genome in vitro and in vivo without evidence of cellular toxicity.