Transduction Efficiency and Immune Response Associated With the Administration of AAV8 Vector Into Dog Skeletal Muscle
Transduction Efficiency and Immune Response Associated With the Administration of AAV8 Vector Into Dog Skeletal Muscle
复制标题
DOI：
10.1038/mt.2008.225
复制
发表时间：
2009-01-01
影响因子：
12.4
通讯作者：
Takeda, Shin'ichi
中科院分区：
文献类型：
--
作者：
Ohshima, Sachiko;Shin, Jin-Hong;Takeda, Shin'ichi
重组腺相关病毒（rAAV）介导的基因转移是治疗杜氏肌营养不良症（DMD）的一种有吸引力的方法。我们研究了在日本正常和犬X连锁肌营养不良症（CXMDJ）犬中与rAAV 2和rAAV 8给药相关的肌肉转导谱和免疫应答。将编码lacZ基因的rAAV 2或rAAV 8注射到正常狗的骨骼肌中。注射后两周，我们检测到rAAV 8转导的犬骨骼肌中的β-半乳糖苷酶阳性纤维比rAAV 2转导的肌肉中的β-半乳糖苷酶阳性纤维数量更多。尽管使用抗CD 4和抗CD 8抗体的免疫组织化学分析显示，与rAAV 2相比，rAAV 8对T细胞的反应更少，但注射rAAV 8的肌肉中β-半乳糖苷酶的表达持续了24小时。
Recombinant adeno-associated virus (rAAV)-mediated gene transfer is an attractive approach to the treatment of Duchenne muscular dystrophy (DMD). We investigated the muscle transduction profiles and immune responses associated with the administration of rAAV2 and rAAV8 in normal and canine X-linked muscular dystrophy in Japan (CXMDJ) dogs. rAAV2 or rAAV8 encoding the lacZ gene was injected into the skeletal muscles of normal dogs. Two weeks after the injection, we detected a larger number of beta-galactosidase-positive fibers in rAAV8-transduced canine skeletal muscle than in rAAV2-transduced muscle. Although immunohistochemical analysis using anti-CD4 and anti-CD8 antibodies revealed less T-cell response to rAAV8 than to rAAV2, beta-galactosidase expression in rAAV8-injected muscle lasted for