诱导多能干细胞技术及其在疾病研究中的应用 【已撤稿】

doi:10.16288/j.yczz.20-235

遗传 ›› 2020, Vol. 42 ›› Issue (11): 1042-1061.doi: 10.16288/j.yczz.20-235

诱导多能干细胞技术及其在疾病研究中的应用【已撤稿】

蔡晨依, 孟飞龙, 饶琳, 刘云玥, 赵小立()

浙江大学生命科学学院遗传与再生生物学研究所,浙江省细胞与基因工程重点研究实验室,杭州 310058

收稿日期:2020-08-12 修回日期:2020-10-19 出版日期:2020-11-20 发布日期:2020-11-03
通讯作者: 赵小立 E-mail:zhaoxiaoli@zju.edu.cn
作者简介:蔡晨依,硕士研究生,专业方向：干细胞分化。E-mail: caichenyii@163.com
基金资助:
国家重点基础研究发展规划项目(973计划)资助编号(2012CB967900)

Induced pluripotent stem cell technology and its application in disease research [Retracted]

Chenyi Cai, Feilong Meng, Lin Rao, Yunyue Liu, Xiaoli Zhao()

Key Research Laboratory for Cell and Gene Engineering of Zhejiang Provincial, Institute of Genetics and Regenerative Biology, College of Life Sciences, Zhejiang University, Hangzhou 310058, China

Received:2020-08-12 Revised:2020-10-19 Online:2020-11-20 Published:2020-11-03
Contact: Zhao Xiaoli E-mail:zhaoxiaoli@zju.edu.cn
Supported by:
Supported by the National Basic Research and Development Program of China (973 Program) No(2012CB967900)

摘要/Abstract

摘要：

自2006年Takahashi和Yamanaka报道生成诱导多能干细胞(induced pluripotent stem cells, iPSCs)以来,多能干细胞领域进入了前所未有的发展状态,在疾病建模、药物发现以及细胞疗法等各方面都发挥重要作用,促进了细胞生物学和再生医学等学科的发展。目前,iPSCs技术已成为研究病理机制的重要工具,利用iPSCs技术筛选的新药物正在研发中,使用iPSCs衍生细胞的临床试验数量也在逐渐增长。iPSCs与基因编辑技术以及3D类器官相结合的最新研究进展促进了iPSCs在疾病研究中的进一步应用。本文介绍了近年来重编程方法的革新,分析了整合病毒载体系统、整合非病毒载体系统、非整合病毒载体系统以及非整合非病毒载体系统四种重编程方法的利弊;同时综述了iPSCs在疾病建模以及临床治疗等方面的最新研究进展,为促进iPSCs各领域的深入研究提供参考。

[本文已经撤稿，撤稿声明]

关键词: iPSCs, 重编程, 疾病建模, 细胞疗法

Abstract:

Since Takahashi and Yamanaka reported the generation of induced pluripotent stem cells (iPSCs) in 2006, the field of pluripotent stem cells has entered an unprecedented state of development. It plays an important role in disease modeling, drug discovery and cell therapy, and promotes the development of cell biology and regenerative medicine. At present, iPSC technology has become an important tool for studying of pathological mechanisms. New drugs screened by iPSC technology are being developed, and the number of clinical trials using iPSC-derived cells is gradually increasing. The latest research progress of iPSCs, combined with gene editing technology and 3D organoid methodology, promotes the further applications of iPSCs in disease research. In this review, we introduce the innovation of reprogramming methods in recent years, analyze the advantages and disadvantages of four reprogramming methods: integrated virus vector system, integrated non-viral vector system, non-integrated virus vector system and non-integrated non virus vector system. At the same time, we summarize the latest research progress on iPSCs in disease modeling and clinical treatment strategies, so as to provide a reference for further in-depth research in various fields of iPSCs.

[This paper has been retracted. ]

Key words: iPSCs, reprogramming, disease modeling, cell therapy

蔡晨依, 孟飞龙, 饶琳, 刘云玥, 赵小立. 诱导多能干细胞技术及其在疾病研究中的应用【已撤稿】[J]. 遗传, 2020, 42(11): 1042-1061.

Chenyi Cai, Feilong Meng, Lin Rao, Yunyue Liu, Xiaoli Zhao. Induced pluripotent stem cell technology and its application in disease research [Retracted][J]. Hereditas(Beijing), 2020, 42(11): 1042-1061.

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系统	酶	作用机理	参考文献
ZFN	锌指核酸酶	定制的锌指蛋白DNA结合模块融合到细菌内切酶FokI的切割域,诱导位点特异性DNA双链断裂(DSB),然后通过NHEJ进行DNA修复以产生小的插入和缺失突变(Indels)或引发HDR以引入精确的核苷酸修饰	[60,61]
TALEN	转录激活因子样效应核酸酶	定制的TALE蛋白DNA结合模块融合到细菌核酸内切酶FokI中,诱导位点特异性DSB,然后通过NHEJ进行DNA修复引入Indels或通过HDR引入特异性DNA突变	[62,63]
CRISPR/Cas9	野生型Cas9,Cas9 核酸内切酶	RNA引导的位点特异性DNA切割触发NHEJ产生Indels或引发HDR来引入精确的DNA修饰	[64]
	Cas9 核酸内切酶	结合Cas9核酸内切酶和配对的sgRNA来诱导位点特异性DSB,成对的切割显著减少了脱靶效应(50到1500倍)	[68]
	eSpCas9	结构导向的蛋白质工程被用来创造spCas9变异体,这种变异体保持对靶点的严格切割的同时显著降低了脱靶效应	[69]
	Cas9-VRER变体	这个被称为“CORRECT”的平台允许以精确的单等位基因或双等位基因的方式引入DNA修饰	[71]
CRISPR/Cas9/ 胞苷脱氨酶	CRISPR/Cas9与胞苷脱氨酶的融合体	碱基编辑方法可以直接将胞苷转化为尿苷,而不需要DSB和供体DNA模板	[72]

诱导多能干细胞技术及其在疾病研究中的应用【已撤稿】

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诱导多能干细胞技术及其在疾病研究中的应用 【已撤稿】

Induced pluripotent stem cell technology and its application in disease research [Retracted]

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诱导多能干细胞技术及其在疾病研究中的应用【已撤稿】