K137R mutation on adeno-associated viral capsids had minimal effect on enhancing gene delivery in vivo.
K137R mutation on adeno-associated viral capsids had minimal effect on enhancing gene delivery in vivo.
复制标题
腺相关病毒衣壳上的 K137R 突变对增强体内基因递送的影响极小。
DOI：
10.1089/hgtb.2013.176
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发表时间：
2014
影响因子：
--
通讯作者：
Xiao,Xiao
中科院分区：
文献类型：
--
作者：
Qiao,Chunping;Li,Chengwen;Zhao,Chunxia;Li,Jianbin;Bian,Tao;Grieger,Joshua;Li,Juan;Samulski,RJude;Xiao,Xiao
腺相关病毒（AAV）载体已经成为基因治疗应用的有吸引力的载体。开发具有增强的基因转导效率的AAV载体对于减轻AAV生产的负担和最小化潜在的免疫应答是重要的。AAV衣壳上的合理突变作为增强AAV转导效率的简单方法已受到关注。最近报道，AAV 1和AAV 8上的单氨基酸突变K137 R使肝脏转基因表达增加5-10倍。为了确定在其他AAV血清型上的相同突变是否会导致类似的基因增强效应，在AAV 7、AAV 8和AAV 9上产生K137 R突变体，并在体内评价它们的效应。利用两个报告基因：由巨细胞病毒启动子驱动的核LacZ基因和由CB启动子驱动的荧光素酶基因。令人惊讶的是，我们发现使用野生型AAV 8衣壳或AAV 8-K137 R在肝脏或其他组织中的荧光素酶基因表达没有差异。AAV 8-K137 R在肝脏中的LacZ基因表达比野生型AAV 8高约一倍。然而，在其他组织中没有发现差异，如骨骼肌和心肌。此外，在AAV 7-K137 R或AAV 9-K137 R突变体的转基因表达中没有发现差异。我们的结果表明，AAV 7、AAV 8和AAV 9上的K137 R突变对体内转导效率具有最小的影响或没有影响。
The adeno-associated viral (AAV) vector has emerged as an attractive vector for gene therapy applications. Development of AAV vectors with enhanced gene transduction efficiency is important to ease the burden of AAV production and minimize potential immune responses. Rational mutations on AAV capsids have gained attention as a simple method of enhancing AAV transduction efficiency. A single-amino acid mutation, K137R, on AAV1 and AAV8 was recently reported to increase liver transgene expression by 5–10-fold. To determine whether the same mutation on other AAV serotypes would result in similar gene enhancement effects, K137R mutants were generated on AAV7, AAV8, and AAV9, and their effects were evaluatedin vivo. Two reporter genes were utilized: the nuclearLacZgene driven by the cytomegalovirus promoter and theluciferasegene driven by the CB promoter. Surprisingly, we found no difference in luciferase gene expression in the liver or other tissues using either the wild-type AAV8 capsid or AAV8-K137R.LacZgene expression in the liver by AAV8-K137R was about onefold higher than that of wild-type AAV8. However, no difference was found in other tissues, such as skeletal muscle and cardiac muscle. In addition, no difference was found in transgene expression with either AAV7-K137R or AAV9-K137R mutants. Our results indicated that the K137R mutation on AAV7, AAV8, and AAV9 had minimal to no effect on transduction efficiencyin vivo.
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影响因子：
12.4
作者：
Petrs-Silva, Hilda;Dinculescu, Astra;Hauswirth, William W.
通讯作者：
Hauswirth, William W.
影响因子：
4.2
作者：
Hauswirth, William W.;Aleman, Tomas S.;Jacobson, Samuel G.
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Jacobson, Samuel G.
影响因子：
20.3
作者：
Manno, CS;Chew, AJ;Glader, B
通讯作者：
Glader, B
影响因子：
12.4
作者：
Pang, Ji-jing;Dai, Xufeng;Hauswirth, William W.
通讯作者：
Hauswirth, William W.
影响因子：
158.5
作者：
Maguire, Albert M.;Simonelli, Francesca;Bennett, Jean
通讯作者：
Bennett, Jean