CRISPR-Cas9基因编辑技术或许并没有我们想象中那么精确

2018年7月25日 讯 /生物谷BIOON/ –如今CRISPR基因编辑技术正在给医学和生物学研究带来革命性的变化,相比以往的基因编辑技术而言,该技术能帮助科学家们以更高的准确性和稳定性来对DNA进行编辑;但最近一项研究报告中就质疑这项基因编辑技术的精准性。

科学家们进行基因编辑就是希望其能够帮助治愈和纠正某些疾病,而且截至目前为止,也已经有很多成功的报道,比如治疗小鼠耳聋、以及修饰细胞来治疗癌症等。目前有17项临床试验正在对人类疾病运用这项基因编辑技术,包括白血病、脑癌和镰刀细胞贫血症。在将CRISPR技术引入到临床中治疗癌症或先天性障碍之前,研究人员就必须解决该技术的安全性和准确性的问题。

CRISPR技术如何再次发挥作用?

CRISPR基因编辑技术能利用分子剪刀Cas9酶来切割我们想要去切割的DNA,随后我们就能够粘贴DNA来替代我们想要移除的DNA信息,Cas9能通过一种特殊的“向导”来识别人类基因组中的特殊DNA片段。Cas9能在机体中存在数小时乃至数周,其在体内能够剪切并且粘贴其它的DNA片段或者DNA目标片段。

最新研究发现了什么

最近一项刊登在国际杂志Nature Biotechnology上的研究报告中,来自桑格研究所的研究人员深入分析了Cas9剪刀的准确性,研究人员想要确定是否Cas9的切割和粘贴过程能够足够准确且安全地应用于人类机体中治疗相关的疾病。为了回答这个重要的问题,研究人员仔细检查了小鼠胚胎干细胞和人类细胞中距离其想要切割的目标片段附近的DNA片段,他们发现,当DNA被修复后(新型DNA粘贴到了被切割的片段上),分子剪刀(Cas9)就能够不断地去剪切DNA片段,于是研究人员就在切割位点附近发现了明显的区域,在这一区域中DNA就能够被移除、重排或倒置。

如果DNA片段被移除或倒置的话,基因的修饰就变得非常危险了,其甚至还会引发疾病,虽然这看起来很害怕,但利用新型的测序技术或许就能够解决这一问题。

能否使用不同的剪刀?

目前解决这个问题有以下几种选择,其中一个选择就是从机体中分离出研究人员想要编辑的细胞,然后重新注入研究人员进行正确编辑过的细胞。比如,研究人员就能从体内分离出对杀死癌细胞至关重要的淋巴细胞(白细胞),随后利用CRISPR技术进行修饰就能增强淋巴细胞的抗癌特性。这些细胞的DNA能被详细测序,而且只有被进行准确特异性基因编辑的细胞才会被选择出来,并且重新输回到患者体内来杀灭癌细胞。

虽然这种策略对于从体内分离出来的细胞是有效的,但一些诸如神经元和肌肉等细胞是无法从体内分离出来的,利用Cas9剪刀就无法对这些类型的细胞进行编辑。值得庆幸的是,研究人员还发现,其它CRISPR系统或许并不需要对DNA进行切割,而有些CRISPR系统仅能对RNA进行切割,而并非是DNA。

RNA在被降解之前,其会在细胞的一段特定的时间内存在,随后才会被降解,这就能帮助研究人员很好地控制CRISPR系统的使用和持续时间,目前研究人员发现,CRISPR基因编辑技术能够成功治疗痴呆症的小鼠,类似地,一些CRISPR系统还能改变DNA的碱基,而并非对其进行切割,这种CRISPR技术就能成功用于纠正诱发某些疾病的特殊突变,比如小鼠的遗传性耳聋等。

简言之,在临床上使用CRISPR技术之前,研究人员还需要深入了解更多Cas9剪刀在细胞中的作用。

316 thoughts on “CRISPR-Cas9基因编辑技术或许并没有我们想象中那么精确”

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