Transcription activator-like effector nuclease-mediated transduction of exogenous gene into IL2RG locus.
Transcription activator-like effector nuclease-mediated transduction of exogenous gene into IL2RG locus.
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DOI：
10.1038/srep05043
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发表时间：
2014-05-23
影响因子：
4.6
通讯作者：
Asahara H
中科院分区：
文献类型：
--
作者：
Matsubara Y;Chiba T;Kashimada K;Morio T;Takada S;Mizutani S;Asahara H
由白介素 2 受体 γ (IL2RG) 基因突变引起的 X 连锁严重联合免疫缺陷 (SCID-X1) 会威胁受影响男孩在生命第一年的生存，除非提供造血干细胞移植。尽管病毒载体介导的基因治疗已在没有 HLA 匹配供体的患者中成功进行，但在一些个体中也报道了由载体介导的插入突变引起的白血病。转录激活剂样效应核酸酶（TALEN）是一种人工序列特异性核酸内切酶，有望彻底改变致病突变的精确校正并消除插入突变的风险。在这里，我们报告了 TALEN 介导的 IL2RG 基因座基因组编辑。我们将 TALEN 与靶向载体一起转染至 Jurkat 细胞中，并确认外源基因精确引入 IL2RG 基因座。此外，我们发现靶向载体中同源臂的长度影响TALEN介导的同源重组的效率。
X-linked severe combined immunodeficiency (SCID-X1) caused by mutations in interleukin 2 receptor gamma (IL2RG) gene threatens the survival of affected boys during the first year of life unless hematopoietic stem cell transplantation is provided. Although viral vector-mediated gene therapy has been successfully performed in patients with no HLA-matched donors, leukemia caused by vector-mediated insertional mutagenesis has been reported in some individuals. Transcription activator-like effector nuclease (TALEN) is an artificial sequence-specific endonuclease that is expected to revolutionize the precise correction of disease-causing mutations and eliminate the risk of insertional mutagenesis. Here, we report TALEN-mediated genome editing of the IL2RG locus. We transfected TALENs along with a targeting vector into Jurkat cells, and we confirmed the precise introduction of the exogenous gene into the IL2RG locus. In addition, we found that the length of homology arm in the targeting vector influenced the efficiency of TALEN-mediated homologous recombination.
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