Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Mol Ther Nucleic Acids. 2013 May 28;2(5):e95. doi: 10.1038/mtna.2013.21.
Profiles of recombinant adeno-associated virus (rAAV)-mediated transduction show interspecies differences for each AAV serotype. Robust long-term transgene expression is generally observed in rodents, whereas insufficient transduction is seen in animals with more advanced immune systems. Non-human primates, including the common marmoset, could provide appropriate models for neuromuscular diseases because of their higher brain functions and physiological resemblance to humans. Strategies to induce pathologies in the neuromuscular tissues of non-human primates by rAAV-mediated transduction are promising; however, transgene expression patterns with rAAV transduction have not been elucidated in marmosets. In this study, transduction of adult marmoset skeletal muscle with rAAV9 led to robust and persistent enhanced green fluorescent protein (EGFP) expression that was independent of the muscle fiber type, although lymphocyte infiltration was recognized. Systemic rAAV injection into pregnant marmosets led to transplacental fetal transduction. Surprisingly, the intraperitoneal injection of rAAV1 and rAAV9 into the neonatal marmoset resulted in systemic transduction and persistent transgene expression without lymphocyte infiltration. Skeletal and cardiac muscle were effectively transduced with rAAV1 and rAAV9, respectively. Interestingly, rAAV9 transduction led to intense EGFP signaling in the axons of the corpus callosum. These transduction protocols with rAAV will be useful for investigating gene functions in the neuromuscular tissues and developing gene therapy strategies.Molecular Therapy-Nucleic Acids (2013) 2, e95; doi:10.1038/mtna.2013.21; published online 28 May 2013.
腺相关病毒（rAAV）介导的转导谱显示每种 AAV 血清型在种间存在差异。在啮齿动物中通常观察到强大的长期转基因表达，而在免疫系统更发达的动物中则观察到转导不足。包括普通狨猴在内的非人类灵长类动物，由于其较高的大脑功能和与人类相似的生理机能，可为神经肌肉疾病提供合适的模型。通过 rAAV 介导的转导在非人类灵长类动物的神经肌肉组织中诱导病理学的策略很有前景；然而，rAAV 转导在狨猴中的转基因表达模式尚未阐明。在这项研究中，rAAV9 转导成年狨猴骨骼肌导致了强大而持久的增强型绿色荧光蛋白（EGFP）表达，这种表达与肌纤维类型无关，尽管观察到淋巴细胞浸润。系统注射 rAAV 到怀孕的狨猴中导致胎儿经胎盘转导。令人惊讶的是，将 rAAV1 和 rAAV9 腹腔内注射到新生狨猴中导致全身转导和持续的转基因表达，而没有淋巴细胞浸润。rAAV1 和 rAAV9 分别有效地转导了骨骼肌和心肌。有趣的是，rAAV9 转导导致胼胝体轴突中强烈的 EGFP 信号。这些 rAAV 的转导方案将有助于研究神经肌肉组织中的基因功能，并开发基因治疗策略。分子治疗-核酸（2013）2, e95；doi:10.1038/mtna.2013.21；在线发表 2013 年 5 月 28 日。
