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Method for Multiple Portal Vein Infusions in Mice: Quantitation of Adenovirus-Mediated Hepatic Gene Transfer

机译:小鼠多次门静脉输注的方法:腺病毒介导的肝基因转移的定量

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摘要

For many preclinical studies, the mouse has been an invaluable model. For hepatic studies, including gene therapy, the use of the mouse has been limited because of the inability to obtain long-term portal vein access. In this study, we have developeda surgical cannula model that allows for repeat portal vein infusion in a noninvasive manner. We have used this model to establish that the tissue distribution of recombinant adenoviral vectors is similar after portal vein or peripheral vein infusion. The majority of the vector -was present in the liver, ranging from 14 to 28 copies per hepatocyte. The second most prevalent tissues were the spleen and lung with 110 less adenoviral DNA The brain and ovaries had the least DNA, 1/1000 less than the liver.Additional studies were performed to study the effects of secondary adenovirus infusion through the portal vein cannula. Permanent portal vein access in a mouse model will be invaluable for a large number of medical studies, including the development ofnew technologies for hepatic gene transfer.
机译:对于许多临床前研究而言,小鼠一直是不可估量的模型。对于肝脏研究,包括基因疗法,由于无法获得长期的门静脉通路而限制了小鼠的使用。在这项研究中,我们开发了一种外科手术插管模型,允许以无创方式重复进行门静脉输注。我们已经使用该模型建立了门静脉或外周静脉输注后重组腺病毒载体的组织分布是相似的。大部分载体存在于肝脏中,每肝细胞从14到28拷贝不等。第二个最普遍的组织是脾脏和肺脏,腺病毒DNA少110个。大脑和卵巢的DNA最少,比肝脏少1/1000。还进行了其他研究,以研究通过门静脉插管进行二次腺病毒输注的效果。小鼠模型中永久性门静脉通路对于许多医学研究而言将是无价的,包括开发肝基因转移的新技术。

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