Efficient transduction of skeletal muscle using vectors based on adeno-associated virus serotype 6
Efficient transduction of skeletal muscle using vectors based on adeno-associated virus serotype 6
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DOI：
10.1016/j.ymthe.2004.07.016
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发表时间：
2004-10-01
影响因子：
12.4
通讯作者：
Chamberlain, JS
中科院分区：
文献类型：
--
作者：
Blankinship, MJ;Gregorevic, P;Chamberlain, JS
基于重组腺相关病毒（rAAV）的载体已经成为将基因转移到骨骼肌的首选工具。rAAV载体表现出有效、安全和稳定的转导。存在多种血清型的AAV，但基于血清型2（rAAV 2）的载体是最彻底表征和经常使用的。在这里，我们的特点转导的骨骼肌肉组织使用rAAV载体假型与血清型6衣壳蛋白（rAAV6）。我们证明，rAAV6载体可以有效地使小鼠的骨骼肌组织达到比rAAV2载体高>500倍的水平，并且在直接注射后可以容易地使个体肌肉饱和。此外，rAAV6载体能够在简单注射到胸腔内后转导小鼠的膈肌和肋间肌肉，并且能够在作为新生幼崽的腹膜内空间注射的小鼠的整个肌肉组织中广泛转导。这些结果表明，rAAV6载体在靶向骨骼肌组织的基因递送方案中具有巨大的潜力。
Vectors based on recombinant adeno-associated viruses (rAAV) have emerged as tools of choice for gene transfer to skeletal muscle. rAAV vectors demonstrate efficient, safe, and stable transduction. Multiple serotypes of AAV exist, but vectors based on serotype 2 (rAAV2) are the most thoroughly characterized and frequently employed. Here, we characterize transduction of the skeletal musculature using rAAV vectors pseudotyped with serotype 6 capsid proteins (rAAV6). We demonstrate that rAAV6 vectors can efficiently transduce the skeletal musculature of mice at levels >500-fold higher than is achievable with rAAV2 vectors and can readily saturate individual muscles following direct injection. Further, rAAV6 vectors are capable of transducing the diaphragm and intercostal muscles of mice after a simple injection into the intrathoracic cavity and are capable of widespread transduction throughout the musculature of mice injected in the intraperitoneal space as newborn pups. These results demonstrate that rAAV6 vectors hold great potential for use in gene delivery protocols targeting the skeletal musculature.