Targeted gene correction of laminopathy-associated LMNA mutations in patient-specific iPSCs.
Targeted gene correction of laminopathy-associated LMNA mutations in patient-specific iPSCs.
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DOI：
10.1016/j.stem.2011.04.019
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发表时间：
2011-06-03
期刊：
影响因子：
23.9
通讯作者：
Izpisua Belmonte, Juan Carlos
中科院分区：
文献类型：
--
作者：
Liu, Guang-Hui;Suzuki, Keiichiro;Qu, Jing;Sancho-Martinez, Ignacio;Yi, Fei;Li, Mo;Kumar, Sachin;Nivet, Emmanuel;Kim, Jessica;Soligalla, Rupa Devi;Dubova, Ilir;Goebl, April;Plongthongkum, Nongluk;Fung, Ho-Lim;Zhang, Kun;Loring, Jeanne F.;Laurent, Louise C.;Izpisua Belmonte, Juan Carlos
基于干细胞的方法与基因编辑技术的结合代表了研究人类疾病和开发疗法的一种有吸引力的策略。然而，迄今为止针对人类细胞描述的基因编辑方法受到技术限制，包括有限的靶基因大小、转录不活跃位点的靶向效率低以及可能阻碍广泛临床应用的脱靶遗传效应。为了解决这些局限性，并作为原理证明，我们重点研究了核纤层蛋白 A (LMNA) 上多个突变的基于同源重组的基因校正，这些突变与各种退行性疾病相关。我们表明，辅助依赖性腺病毒载体（HDAdV）为纠正人类诱导多能干细胞中大基因组区域的突变提供了一种高效且安全的方法，并且对成人间充质干细胞也有效。这种方法可用于生成基因型匹配的细胞系，用于疾病建模和药物发现，也可能用于治疗。
Combination of stem cell-based approaches with gene-editing technologies represents an attractive strategy for studying human disease and developing therapies. However, gene-editing methodologies described to date for human cells suffer from technical limitations including limited target gene size, low targeting efficiency at transcriptionally inactive loci, and off-target genetic effects that could hamper broad clinical application. To address these limitations, and as a proof of principle, we focused on homologous recombination-based gene correction of multiple mutations on lamin A (LMNA), which are associated with various degenerative diseases. We show that helper-dependent adenoviral vectors (HDAdVs) provide a highly efficient and safe method for correcting mutations in large genomic regions in human induced pluripotent stem cells and can also be effective in adult human mesenchymal stem cells. This type of approach could be used to generate genotype-matched cell lines for disease modeling and drug discovery and potentially also in therapeutics.
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影响因子：
46.9
作者：
Hockemeyer, Dirk;Soldner, Frank;Beard, Caroline;Gao, Qing;Mitalipova, Maisam;DeKelver, Russell C.;Katibah, George E.;Amora, Ranier;Boydston, Elizabeth A.;Zeitler, Bryan;Meng, Xiangdong;Miller, Jeffrey C.;Zhang, Lei;Rebar, Edward J.;Gregory, Philip D.;Urnov, Fyodor D.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
64.8
作者：
MANSOUR, SL;THOMAS, KR;CAPECCHI, MR
通讯作者：
CAPECCHI, MR
影响因子：
82.9
作者：
Scaffidi, P;Misteli, T
通讯作者：
Misteli, T
DOI：
10.1016/j.bbrc.2009.08.075
发表时间：
2009-10-30
影响因子：
3.1
作者：
Mitsui, Kaoru;Suzuki, Keiichiro;Mitani, Kohnosuke
通讯作者：
Mitani, Kohnosuke
影响因子：
12.4
作者：
Khan, Iram F.;Hirata, Roli K.;Russell, David W.
通讯作者：
Russell, David W.