Cancer Discovery：细胞对CRISPR的应答不容忽视

2016-06-10 叶子生物通

这两年几乎人人都在谈论CRISPR基因组编辑，那么细胞对这个系统的闯入作何感想呢？Cancer Discovery杂志最近发表的一项研究指出，细胞会对CRISPR-Cas9产生一种不容忽视的应答。细菌一直在与病毒或入侵核酸进行斗争，为此它们演化出了多种防御机制，CRISPR-Cas适应性免疫系统就是其中之一。规律成簇的间隔短回文重复CRISPR与内切酶Cas9的组合，可以在引导RNA的指引

这两年几乎人人都在谈论CRISPR基因组编辑，那么细胞对这个系统的闯入作何感想呢？Cancer Discovery杂志最近发表的一项研究指出，细胞会对CRISPR-Cas9产生一种不容忽视的应答。

细菌一直在与病毒或入侵核酸进行斗争，为此它们演化出了多种防御机制，CRISPR-Cas适应性免疫系统就是其中之一。规律成簇的间隔短回文重复CRISPR与内切酶Cas9的组合，可以在引导RNA的指引下，靶标并切割入侵者的遗传物质。这种特性使CRISPR系统成为了基因组编辑和基因功能研究的实用工具。

CRISPR-Cas9能够很方便的在哺乳动物细胞中进行体细胞遗传筛选。但哈佛大学Dana-Farber癌症研究所的科学家们在实践中发现，CRISPR-Cas9靶标会使细胞产生一种不依赖基因的应答。而这种应答会干扰人们对CRISPR筛选数据的解读。

为了鉴定增殖的必需基因，研究人员用CRISPR-Cas9在33个癌细胞系中进行了全基因组的功能缺失筛选。他们发现，基因组编辑之后的基因拷贝数增加和细胞活力下降有很强的关联。

在拷贝数增加的区域中，CRISPR-Cas9靶标会诱导G2细胞周期停滞，由此显著减少癌细胞的增殖。这项研究表明，被CRISPR-Cas9靶标的基因组引起了不依赖基因的抗增殖细胞应答。理解这种影响对于正确解读CRISPR-Cas9筛选数据非常重要。

基因筛选是经典的生物学研究方法，常用于鉴定在生物学过程中起作用的基因。十多年来RNAi一直是这一领域的王者，然而新兴技术的涌现（尤其是CRISPR技术）正在逐渐瓦解RNAi的统治地位。那么，在RNAi和CRISPR筛选之间我们究竟应该如何抉择呢？斯坦福大学的研究人员对这两种技术进行了全面比较，并将研究结果发表在Nature Biotechnology杂志上。

原始出处

Andrew J. Aguirre1, Robin M. Meyers2, Barbara A. Weir1, Francisca Vazquez1.et.al.Genomic copy number dictates a gene-independent cell response to CRISPR-Cas9 targeting.Cancer Discovery.2016

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2017-01-29 cmj8wellington

#Dis#

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2016-10-07 yahu

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2016-06-12 yuandd

#CRISPR#

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2016-06-12 yankaienglish

#ISC#

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2016-06-11 sygao2002

肿瘤免疫研究大有发展

149 0
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2016-06-10 milkshark

值得研究

148 0
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2016-06-10 milkshark

的确这样

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