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腺病毒重组体对成年与新生小鼠组织的短期转导效率差异

Differential short-term transduction efficiency of adult versus newborn mouse tissues by adenoviral recombinants.

作者信息

Huard J, Lochmüller H, Acsadi G, Jani A, Holland P, Guérin C, Massie B, Karpati G

机构信息

Montreal Neurological Institute, McGill University, Quebec, Canada.

出版信息

Exp Mol Pathol. 1995 Apr;62(2):131-43. doi: 10.1006/exmp.1995.1015.

Abstract

We demonstrated different transduction efficiency in several major organs of the immature (newborn) versus mature (adult) mice using adenoviral recombinants containing expression cassettes for either firefly luciferase or bacterial beta-galactosidase reporter genes. The studied tissues included skeletal muscle, heart, brain, lung, kidney, and liver. The transduction efficiency in all tissues, especially skeletal muscle, was significantly less in adults than in newborns, with two exceptions. In the heart, transduction efficiency was the same in newborns and adults, while in brain, it was greater in the adult than in the newborn. The cited differences in transduction efficiencies between newborn and adult tissues applied approximately equally to both reporter genes. The alpha v integrin level showed the same trend as the transduction efficiency in all tissues, except the heart. Polymerase chain reaction showed a specific adenoviral product in proportion to the reporter gene expression in muscle, heart, and brain. The results of this study should be considered in designing gene therapy strategies in genetic diseases.

摘要

我们使用含有萤火虫荧光素酶或细菌β-半乳糖苷酶报告基因表达盒的腺病毒重组体,在未成熟(新生)和成熟(成年)小鼠的几个主要器官中展示了不同的转导效率。所研究的组织包括骨骼肌、心脏、大脑、肺、肾脏和肝脏。除两个例外情况外,所有组织(尤其是骨骼肌)中的转导效率在成年小鼠中显著低于新生小鼠。在心脏中,新生小鼠和成年小鼠的转导效率相同,而在大脑中,成年小鼠的转导效率高于新生小鼠。新生和成年组织中转导效率的上述差异对两种报告基因大致同样适用。除心脏外,αv整合素水平在所有组织中与转导效率呈现相同趋势。聚合酶链反应显示,在肌肉、心脏和大脑中,有与报告基因表达成比例的特异性腺病毒产物。在设计针对遗传疾病的基因治疗策略时,应考虑本研究的结果。

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