Comparative cardiac gene delivery of adeno-associated virus serotypes 1-9 reveals that AAV6 mediates the most efficient transduction in mouse heart.
Comparative cardiac gene delivery of adeno-associated virus serotypes 1-9 reveals that AAV6 mediates the most efficient transduction in mouse heart.
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DOI：
10.1111/j.1752-8062.2010.00190.x
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Rabinowitz JE
中科院分区：
文献类型：
--
作者：
Zincarelli C;Soltys S;Rengo G;Koch WJ;Rabinowitz JE
心脏基因转移是开发新的心脏病治疗方法的一种有吸引力的工具。腺相关病毒（AAV）载体被广泛用于介导动物模型中的转基因表达，并正在评估人类基因治疗。然而，目前尚不清楚哪种血清型显示最佳的心肌向性。因此，我们进行了这项研究，以直接比较间接冠状动脉内注射后AAV血清型1-9心脏转导效率。在交叉夹闭升主动脉和肺动脉后，将AAV-CMV-荧光素酶血清型1-9注射到成年小鼠的左心室腔中。在注射后3-7-21-70-140天，使用成像系统可视化荧光素酶表达。在第140天进行超声心动图以评价心脏功能。在研究结束时，在几种组织中评估了不同AAV血清型的荧光素酶活性和基因组拷贝，并通过对巨噬细胞和淋巴细胞抗原染色在心脏切片上评价了潜在的AAV免疫原性。在AAV血清型1-9中，AAV 6显示出以组织特异性方式在心肌中实现高转导水平的最佳能力，而其他血清型具有较少的心脏转导和更多的心脏外表达，特别是在肝脏中。重要的是，用该标记基因测试的血清型均不影响心脏功能，也不与炎症相关。
Cardiac gene transfer is an attractive tool for developing novel heart disease treatments. Adeno-associated viral (AAV) vectors are widely used to mediate transgene expression in animal models and are being evaluated for human gene therapy. However, it is not clear which serotype displays the best cardiac tropism. Therefore, we curried out this study to directly compare AAV serotypes 1–9 heart transduction efficiency after indirect intracoronary injection. AAV-CMV-luciferase serotypes 1–9 were injected in the left ventricular cavity of adult mice, after cross-clamping the ascending aorta and pulmonary artery. An imaging system was used to visualize luciferase expression at 3-7-21-70-140 days post-injection. Echocardiography was performed to evaluate cardiac function on day 140. At the end of the study luciferase enzyme activity and genome copies of the different AAV serotypes were assessed in several tissues and potential AAV immunogenicity was evaluated on heart sections by staining for macrophage and lymphocyte antigens. Among AAV serotypes 1–9, AAV6 showed the best capability of achieving high transduction levels in the myocardium in a tissue-specific manner, whereas the other serotypes owned less cardiac transduction and more extra-cardiac expression, especially in the liver. Importantly, none of the serotypes tested with this marker gene affected cardiac function nor was associated with inflammation.
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影响因子：
20.1
作者：
Pacak, Christina A.;Mah, Cathryn S.;Byrne, Barry J.
通讯作者：
Byrne, Barry J.
DOI：
10.1152/ajpheart.01009.2003
发表时间：
2004-07-01
影响因子：
4.8
作者：
Roth, DM;Lai, NC;Hammond, HK
通讯作者：
Hammond, HK
DOI：
10.1073/pnas.182412299
发表时间：
2002-09-03
影响因子：
11.1
作者：
Gao, GP;Alvira, MR;Wilson, JM
通讯作者：
Wilson, JM
影响因子：
37.8
作者：
LIN, H;PARMACEK, MS;LEIDEN, JM
通讯作者：
LEIDEN, JM
影响因子：
12.4
作者：
Inagaki, Katsuya;Fuess, Sally;Nakai, Hiroyuki
通讯作者：
Nakai, Hiroyuki