凝血因子 X 介导 5 型腺病毒在非人类灵长类动物（小家鼠）肝脏中的基因转移。
Coagulation factor X mediates adenovirus type 5 liver gene transfer in non-human primates (Microcebus murinus).
机构信息
Division of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
出版信息
Gene Ther. 2012 Jan;19(1):109-13. doi: 10.1038/gt.2011.87. Epub 2011 Jun 16.
Abstract
Coagulation factor X (FX)-binding ablated adenovirus type 5 (Ad5) vectors have been genetically engineered to ablate the interaction with FX, resulting in substantially reduced hepatocyte transduction following intravenous administration in rodents. Here, we quantify viral genomes and gene transfer mediated by Ad5 and FX-binding-ablated Ad5 vectors in non-human primates. Ad5 vectors accumulated in and mediated gene transfer predominantly to the liver, whereas FX-binding-ablated vectors primarily targeted the spleen but showed negligible liver gene transfer. In addition, we show that Ad5 binding to hepatocytes may be due to the presence of heparan sulfate proteoglycans (HSPGs) on the cell membrane. Therefore, the Ad5-FX-HSPG pathway mediating liver gene transfer in rodents is also the mechanism underlying Ad5 hepatocyte transduction in Microcebus murinus.
摘要
已将凝血因子 X (FX) 结合缺失的腺病毒 5 型 (Ad5) 载体基因工程改造为消除与 FX 的相互作用，从而导致静脉内给药后啮齿动物的肝细胞转导大大减少。在这里，我们定量分析了非人类灵长类动物中 Ad5 和 FX 结合缺失的 Ad5 载体介导的病毒基因组和基因转移。Ad5 载体在体内积累并主要介导基因转移至肝脏，而 FX 结合缺失的载体主要靶向脾脏，但肝脏基因转移可忽略不计。此外，我们还表明，Ad5 与肝细胞的结合可能是由于细胞膜上存在硫酸乙酰肝素蛋白聚糖 (HSPGs)。因此，介导啮齿动物肝脏基因转移的 Ad5-FX-HSPG 途径也是介导 Microcebus murinus 中 Ad5 肝细胞转导的机制。
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本文引用的文献
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PLoS Pathog. 2010 Oct 7;6(10):e1001142. doi: 10.1371/journal.ppat.1001142.
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