Editing the genome of hiPSC with CRISPR/Cas9: disease models.
Editing the genome of hiPSC with CRISPR/Cas9: disease models.
复制标题
使用CRISPR/CAS9编辑HIPSC的基因组：疾病模型。
DOI：
10.1007/s00335-017-9684-9
复制
发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Bassett AR
中科院分区：
文献类型：
--
作者：
Bassett AR
人类诱导多能干细胞（hiPSC）技术的出现提供了一个独特的机会，从个体患者建立疾病的细胞模型，并研究潜在的遗传畸变对多种不同细胞类型的影响，其中许多通常是不可访问的。将其与基因组编辑技术的最新进展（例如成簇的规则间隔短回文重复序列（CRISPR）系统）相结合，提供了修复患者细胞系中推定的致病等位基因或将疾病等位基因引入健康“WT”细胞系中的能力。这使得能够分析在单一遗传变化中不同的同基因细胞对，这允许对由这种异常导致的分子和细胞表型进行彻底评估。重要的是，这确定了真正的致病性病变，这往往是不可能确定的，从人类遗传研究本身。这些等基因细胞系不仅可用于了解疾病突变的细胞后果，而且还可用于进行高通量遗传和药理学筛选，以了解潜在的病理机制并开发新的治疗剂来预防或治疗此类疾病。在未来，优化和开发这种遗传操作技术可能有助于提供细胞或分子基因疗法，以干预并最终治愈许多使人衰弱的遗传疾病。
The advent of human-induced pluripotent stem cell (hiPSC) technology has provided a unique opportunity to establish cellular models of disease from individual patients, and to study the effects of the underlying genetic aberrations upon multiple different cell types, many of which would not normally be accessible. Combining this with recent advances in genome editing techniques such as the clustered regularly interspaced short palindromic repeat (CRISPR) system has provided an ability to repair putative causative alleles in patient lines, or introduce disease alleles into a healthy “WT” cell line. This has enabled analysis of isogenic cell pairs that differ in a single genetic change, which allows a thorough assessment of the molecular and cellular phenotypes that result from this abnormality. Importantly, this establishes the true causative lesion, which is often impossible to ascertain from human genetic studies alone. These isogenic cell lines can be used not only to understand the cellular consequences of disease mutations, but also to perform high throughput genetic and pharmacological screens to both understand the underlying pathological mechanisms and to develop novel therapeutic agents to prevent or treat such diseases. In the future, optimising and developing such genetic manipulation technologies may facilitate the provision of cellular or molecular gene therapies, to intervene and ultimately cure many debilitating genetic disorders.
登录
查看更多内容
有条件和可逆基因敲除一步的一代。
影响因子：
48
作者：
Andersson-Rolf A;Mustata RC;Merenda A;Kim J;Perera S;Grego T;Andrews K;Tremble K;Silva JC;Fink J;Skarnes WC;Koo BK
通讯作者：
Koo BK
影响因子：
8.8
作者：
Chang, Chia-Wei;Lai, Yi-Shin;Townes, Tim M.
通讯作者：
Townes, Tim M.
影响因子：
46.9
作者：
Cho, Seung Woo;Kim, Sojung;Kim, Jin-Soo
通讯作者：
Kim, Jin-Soo
DOI：
10.1126/science.1245296
发表时间：
2013-11-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chung CY;Khurana V;Auluck PK;Tardiff DF;Mazzulli JR;Soldner F;Baru V;Lou Y;Freyzon Y;Cho S;Mungenast AE;Muffat J;Mitalipova M;Pluth MD;Jui NT;Schüle B;Lippard SJ;Tsai LH;Krainc D;Buchwald SL;Jaenisch R;Lindquist S
通讯作者：
Lindquist S
影响因子：
14.9
作者：
Brinkman EK;Chen T;Amendola M;van Steensel B
通讯作者：
van Steensel B