DNA依赖性蛋白激酶对骨骼肌中重组腺相关病毒2型（rAAV2）基因组分子命运的影响。
Effect of DNA-dependent protein kinase on the molecular fate of the rAAV2 genome in skeletal muscle.
作者信息
Song S, Laipis P J, Berns K I, Flotte T R
机构信息
Genetics Institute, Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610, USA.
出版信息
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4084-8. doi: 10.1073/pnas.061014598. Epub 2001 Mar 13.
Abstract
We report here that the DNA-dependent protein kinase (DNA-PK) affects the molecular fate of the recombinant adeno-associated virus (rAAV) genome in skeletal muscle. rAAV-human alpha1-antitrypsin (rAAV-hAAT) vectors were delivered by intramuscular injection to either C57BL/6 (DNA-PKcs(+)) or C57BL/6-SCID [severe combined immunodeficient (SCID), DNA-PKcs(-)] mice. In both strains, high levels of transgene expression were sustained for up to 1 year after a single injection. Southern blot analysis showed that rAAV genomes persisted as linear episomes for more than 1 year in SCID mice, whereas only circular episomal forms were observed in the C57BL/6 strain. These results indicate that DNA-PK is involved in the formation of circular rAAV episomes.
摘要
我们在此报告，DNA依赖性蛋白激酶（DNA-PK）影响重组腺相关病毒（rAAV）基因组在骨骼肌中的分子命运。通过肌肉注射将rAAV-人α1-抗胰蛋白酶（rAAV-hAAT）载体递送至C57BL/6（DNA-PKcs(+)）或C57BL/6-SCID [严重联合免疫缺陷（SCID），DNA-PKcs(-)]小鼠。在这两种品系中，单次注射后高水平的转基因表达可持续长达1年。Southern印迹分析表明，rAAV基因组在SCID小鼠中以线性附加体形式持续存在超过1年，而在C57BL/6品系中仅观察到环状附加体形式。这些结果表明，DNA-PK参与环状rAAV附加体的形成。
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