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首页> 外文期刊>Gene Therapy and Molecular Biology >An in vivo investigation on the effect of gene-delivered human serine hydrolase KIAA1363 on chemical warfare nerve agent intoxication
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An in vivo investigation on the effect of gene-delivered human serine hydrolase KIAA1363 on chemical warfare nerve agent intoxication

机译：基因传递人丝氨酸水解酶KIAA1363对化学战神经毒剂中毒作用的体内研究

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The ability of human serine hydrolase KIAA1363 as a chemical warfare nerve agentdetoxifying enzyme was investigated in vivo in mice. Using an adenovirus containing the gene for human KIAA1363, the enzyme was expressed as a fusion protein with a hemaglutinin tag (Ad-KIAA1363-HA) in vitro in HEK-293A cells and in vivo in mice. Recombinant KIAA1363 (rKIAA1363-HA) expressed in vitro in HEK-293A cells is membrane-associated with a molecular weight of ~50 kDa. Following intravenous injection of Ad-KIAA1363-HA into mice, rKIAA1363-HA expression was observed in liver and diaphragm but not in circulation or in any other tissues. Expression of the enzyme was first noted on day 2 post-virus injection, reached peak levels on day 4 and declined thereafter. Compared to the livers of control virus- injected mice, the livers of mice injected with Ad-KIAA1363-HA contained ~25-50-folds higher levels of rKIAA1363-HA on day 4. Despite such high levels of rKIAA1363-HA in their livers, mice challenged with lethal doses of diisopropylfluorophosphate, VX or soman did not gain any protection relative to control animals. These results suggest that wild-type human KIAA1363 is not a suitable enzyme for development as a pretreatment candidate against chemical warfare nerve agents.
机译：在小鼠体内研究了人丝氨酸水解酶KIAA1363作为化学战神经毒剂解毒酶的能力。使用含有人KIAA1363基因的腺病毒，该酶在体外HEK-293A细胞中和在小鼠体内表达为带有血凝素标签的融合蛋白（Ad-KIAA1363-HA）。 HEK-293A细胞中体外表达的重组KIAA1363（rKIAA1363-HA）与膜相关，分子量约为50 kDa。在向小鼠静脉内注射Ad-KIAA1363-HA之后，在肝脏和KI肌中观察到rKIAA1363-HA表达，但在循环或其他任何组织中均未观察到。该酶的表达首先在病毒注射后的第2天注意到，在第4天达到峰值，然后下降。与注射对照病毒的小鼠肝脏相比，在第4天注射Ad-KIAA1363-HA的小鼠肝脏中rKIAA1363-HA的含量高约25-50倍，尽管其肝脏中rKIAA1363-HA的含量如此之高，用致死剂量的二异丙基氟磷酸，VX或梭曼攻击的小鼠相对于对照动物没有任何保护作用。这些结果表明，野生型人KIAA1363不适合作为抗化学战神经制剂的预处理候选物进行开发。

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