2项研究显示CRISPR可能会增加编辑细胞的癌症风险

StephenW

2 studies show CRISPR might drive up cancer risk in edited cells
by Amirah Al Idrus |Jun 12, 2018 9:38am



A pair of studies published Monday found that CRISPR editing triggers a mechanism that protects cells from DNA damage. Cells that have this protective system are harder to edit, while cells lacking it are easier to edit. (MIT)


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Off-target, or unintended, editing is a key safety concern of CRISPR-Cas9, as it can lead to cancer and other side effects. Two new studies show that CRISPR editing could raise the risk of targeted cells—those being edited to treat disease—developing tumors.
A pair of studies published Monday found that CRISPR editing triggers a mechanism that protects cells from DNA damage. Cells that have this protective system are harder to edit, while cells lacking it are easier to edit. The catch? Cells that are easy to edit could be more susceptible to cancer-causing mutations.


“We managed to edit cancer cells easily, but when we tried to edit normal, healthy cells, very little happened,” said Emma Haapaniemi, of the Karolinska Institutet in Sweden. What’s more, about half of all cancer cells do not have this protective pathway, the researchers said.
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“When we looked at this further, we found that cutting the genome with CRISPR-Cas9 induced the activation of a protein known as p53, which acts like a cell’s alarm system, signalling that DNA is damaged, and opens the cellular ‘first aid kit’ that repairs damage to the DNA. The triggering of this system makes editing much more difficult,” said Haapaniemi, the first author of one of the studies, published in Nature Medicine. The other study, by Novartis, came to similar conclusions.
Editing cells without this “alarm system” could eventually boost the number of cells without protection against DNA damage. Blocking p53 in healthy cells slated for editing might be one way to “decrease the risk of selecting for p53-deficient cells,” but it could still open them up temporarily to mutations that cause cancer.
RELATED: MIT scientists propose a safer way to edit genes with CRISPR
The news drove down stocks for CRISPR biotechs—CRISPR Therapeutics, Editas and Intellia, to name a few. And while the researchers are calling for more work to determine whether CRISPR editing “may inadvertently raise cancer risk in cells,” they also said it’s hardly time to panic. After all, CRISPR has weathered a couple of storms, including a 2017 study saying the technology caused masses of off-target effects that was retracted this year.
“We don’t want to sound alarmist, and are not saying that CRISPR-Cas9 is bad or dangerous. This is clearly going to be a major tool for use in medicine, so it’s important to pay attention to potential safety concerns. Like with any medical treatment, there are always side effects or potential harm and this should be balanced against the benefits of the treatment,” said Jussi Taipale, of the University of Cambridge, who led the work while at the Karolinska Institutet.

StephenW

2项研究显示CRISPR可能会增加编辑细胞的癌症风险
由Amirah Al Idrus | 2018年6月12日上午9:38
CRISPR纳米颗粒
周一发布的一对研究发现，CRISPR编辑触发了一种保护细胞免受DNA损伤的机制。具有这种保护系统的细胞更难编辑，而缺乏细胞的细胞更容易编辑。 （MIT）


非目标编辑是CRISPR-Cas9的一个关键安全问题，因为它可能导致癌症和其他副作用。两项新的研究表明，CRISPR编辑可能会增加靶细胞的风险 - 那些正在编辑的细胞用于治疗疾病发展的肿瘤。

周一发布的一对研究发现，CRISPR编辑触发了一种保护细胞免受DNA损伤的机制。具有这种保护系统的细胞更难编辑，而缺乏细胞的细胞更容易编辑。赶上？易于编辑的细胞可能更容易受到致癌突变的影响。

“我们设法很容易地编辑癌细胞，但是当我们试图编辑正常的，健康的细胞时，很少发生，”瑞典卡罗林斯卡研究所的艾玛哈帕涅米说。更重要的是，大约一半的癌细胞没有这种保护途径，研究人员说。


“当我们进一步观察时，我们发现用CRISPR-Cas9切割基因组可诱导一种称为p53的蛋白质的激活，该蛋白质就像细胞的警报系统一样，表明DNA被破坏，并打开细胞'急救箱'修复对DNA的破坏。这种系统的触发使得编辑变得更加困难，“哈帕涅米说，他是自然医学杂志发表的一篇研究的第一作者。诺华的另一项研究得出了类似的结论。

没有这个“警报系统”编辑细胞可能最终增加细胞的数量，而没有保护DNA损伤。在定位为编辑的健康细胞中阻断p53可能是“降低选择p53缺陷型细胞的风险”的一种方式，但它仍然可以暂时将其打开导致癌症的突变。

相关：麻省理工学院的科学家们提出了一种用CRISPR编辑基因的更安全的方法

这一消息令CRISPR生物科技CRISPR Therapeutics，Editas和Intellia等股票下跌。虽然研究人员呼吁进行更多的工作以确定CRISPR编辑是否“可能无意中增加细胞癌症风险”，但他们也表示现在几乎没有时间恐慌。毕竟，CRISPR经历了几场风暴，其中包括2017年的一项研究，称该技术引起了今年收回的大量脱靶效应。

“我们不想声音危言耸听，并不是说CRISPR-Cas9是坏的或危险的。这显然将成为医学应用的主要工具，因此重视潜在的安全问题非常重要。就像任何医学治疗一样，总会有副作用或潜在的伤害，这应该与治疗的好处相平衡，“剑桥大学的Jussi Taipale说，他在卡罗林斯卡研究所工作期间领导了这项工作。