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CRISPR革命的下一站

spoon 于 2016-10-13 11:26 发表 [复制链接]

CRISPR革命的下一站

CRISPR革命的下一站

George M. Church是哈佛医学院著名的遗传学教授、Wyss研究所的核心成员,被誉为是个人基因组学和合成生物学的先锋。1984年,Church和 Walter Gilbert发表了首个直接基因组测序方法,一些策略现在仍应用在二代测序技术中。此外,他还发明了多重化分子技术和条码式标签,并作为纳米孔测序技术 的发明者之一。

2014年9月,George M. Church教授领导哈佛医学院的团队,开发了单分子互作测序(SMI-Seq)技术,该技术能够实现单分子水平上的并行分析,获得大量蛋白质的互作图谱。相关阅读:遗传学大牛Nature发表新技术:单分子互作测序。随后的11月,他领导哈佛医学院的团队,在人iPS细胞中进行了CRISPR基因编辑。他们将全基因组测序和靶向深度测序结合起来,鉴定了Cas9编辑iPS细胞时的脱靶效应,还鉴定了一个影响Cas9特异性的单核苷酸变异(SNV)。这项研究发表在Nature Communications杂志上。

就基因表达而言,人们主要还是一次研究一个基因。去年3月,哈佛大学Wyss研究所的研究人员在George Church的领导下利用CRISPR/Cas9系统开发了一种革命性技术。该技术可以揭示一连串基因回路对生物过程的影响,也可以精确指导干细胞分化,生成再生医学所需的移植器官。相关阅读:著名遗传学家获重要突破:Cas9随心所欲地激活基因。随后的7月份,该研究小组开发出了一种预测软件,可以准确找出最有效的方法利用CRISPR-Cas9基因编辑技术来实现基因打靶。这项重要的研究成果发布在《自然方法》(Nature methods)杂志上。

2016年6月1日,George Church以通讯作者身份,在国际著名期刊《The FEBS Journal》发表题为“Next stop for the CRISPR revolution: RNA guided epigenetic regulators”的综述文章,畅谈CRISPR这项革命性技术的下一站:RNA引导的表观遗传学调节因子。

CRISPR和CRISPR相关的Cas蛋白,为便宜的,可编程的、和有效的序列特异性DNA打靶,提供了一个突破性的平台。CRISPR-Cas 系统通过它天然的核酸酶活性,被自然装备到靶向DNA上。因此,致力于各种各样生物的研究小组,迅速采用该技术,开创性地应用到20多个不同物种的基因组 序列编辑当中。然而,生命的生物学代码不仅编码在遗传学中,而且也编码在表观遗传学中。

虽然基因序列编辑是一种强大的能力,但是,我们必须也能够编辑和调控转录和表观遗传学代码。受到早期序列特异性靶向技术(例如ZFs和TALEs)的启发,研究人员迅速将CRISPR-Cas9工具箱扩展到包括转录激活、抑制和表观遗传学修饰。

在这篇综述文章中,作者突出强调了将CRISPR-Cas9工具箱扩展用于转录和表观遗传学调控所取得的进展,也讨论了这些工具的最佳实践指南,以及对于其的未来应用做了展望。

综述最后,作者总结道,CRISPR和Cas9为基础的工具,已经满足了基因组编辑以及表观遗传学调控所需要的一个有效的、可编程的、容易使用的平 台。因此,这个领域正在快速发展,并快速发现新的方法来适应这个系统,以及发现新的规则来提高这些工具的效率。这些工具开辟了快速大规模基因组扫描以发现 功能获得和功能缺失的可能性,以前所未有的深度和精度绘制出功能性网络。
虽然基于CRISPR的转录和表观遗传学调节因子,还有几个方面仍有待于表征,例如这些工具的相对优势、脱靶活性的确切水平以及体内传递这些工具的能力。但是,研究人员仍然预见到将有许多激动人心的应用,例如通过调节内源性位点上的表 达,探测新类别的非编码基因功能,以及应用于人类基因治疗的新范式。

共 3 个关于CRISPR革命的下一站的回复 最后回复于 2017-1-16 12:06

发表于 2017-1-14 23:20:35 | 显示全部楼层

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发表于 2017-1-15 17:17:57 | 显示全部楼层

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发表于 2017-1-16 12:06:49 | 显示全部楼层

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