Transfer of full-length Dmd to the diaphragm muscle of Dmdmdx/mdx mice through systemic administration of plasmid DNA
Transfer of full-length Dmd to the diaphragm muscle of Dmdmdx/mdx mice through systemic administration of plasmid DNA
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DOI：
10.1006/mthe.2001.0419
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发表时间：
2001-07-01
影响因子：
12.4
通讯作者：
Huang, L
中科院分区：
文献类型：
--
作者：
Liu, F;Nishikawa, M;Huang, L
编码抗肌营养不良蛋白（肌肉中的一种大型细胞骨架蛋白）的基因突变会导致杜氏肌营养不良症 (DMD)。受影响的个体经常死于主要由膈肌退化引起的呼吸衰竭。在这里，我们报告了一种将全长肌营养不良蛋白 cDNA 转移到 Dmd(mdx/mdx) 小鼠膈肌中的新方法，该小鼠携带肌营养不良蛋白基因 (Dmd) 突变。静脉注射裸露质粒DNA，随后短暂（八秒）阻断腔静脉血流后，发现了显着的基因转移。这是通过全身施用裸质粒 DNA 将基因转移到膈肌的首次演示。该方法在治疗 DMD 方面具有潜在的应用前景。
Mutations in the gene encoding dystrophin, a large cytoskeletal protein in muscle, lead to Duchenne muscular dystrophy (DMD). Affected individuals often die of respiratory failure resulting primarily from diaphragm muscle degeneration. Here we report a new procedure to transfer the full-length dystrophin cDNA into the diaphragm muscle of Dmd(mdx/mdx) mice, which carry a mutation in the dystrophin gene (Dmd). Significant gene transfer was found after intravenous injection of naked plasmid DNA followed by a brief (eight second) occlusion of blood flow at the vena cava. This is the first demonstration of gene transfer into the diaphragm muscle through systemic administration of naked plasmid DNA. The approach has potential application for treatment of DMD.