相关内容

最新信息

最新关注

基因编辑技术突破!研究人员发现比Cas9更好用的CRISPR酶

  CRISPR基因编辑工具可能是几十年来最重要的医学突破之一,但仍有很大的改进空间。尽管Cas9是基因编辑的首选酶,但这并不意味着它必然是最好的选择。现在,包括CRISPR的共同创造者在内的一个科学家小组已经设计了一种更精确的酶,称为Cas12b。
  CRISPR像一把剪刀一样在基因组上工作,允许科学家针对特定的DNA序列 - 比如那些能提高某些疾病几率的DNA序列 - 然后将它们剪掉并用更有益的基因取而代之。 Cas9酶传统上通过与靶标结合并进行所需的编辑来完成繁重的工作。
  但它并非完美无瑕。过去人们一直担心Cas9不够挑剔,有可能在基因组的其他部分引起意外的突变,并可能增加患者的癌症风险。尽管一些指出这些问题的研究后来被撤回,但如果有更安全的选择,研究替代方案仍然不是一个坏主意。
  Cas12b可能只适合这个账单。研究人员表示,新酶较小,可以比Cas9更精确地归巢于目标,并且通过编辑原代人类T细胞证明了它的实力。作为免疫系统的步兵,微调这些细胞可以改善一系列免疫治疗。
  “这进一步证明有许多有用的CRISPR系统等待发现,”该研究的第一作者Jonathan Strecker说。
  虽然Cas12b早在2015年就被确定为CRISPR候选药物,但它并不容易实现。这种酶来自喜欢火山和深海热液喷口等热环境的细菌,因此它的温度高于人体。为了找到一个可以在凉爽条件下工作的版本,该团队扫描了数千种细菌的基因序列,最终定居在一种名为Bacillus hisashii的虫子中。
  为了加快进度,研究人员自由地向各地的学术团队开放了CRISPR-Cas12b系统。
  该研究发表在Nature Communications杂志上。
来源:麻省理工学院

英文版(原文)
New CRISPR enzyme makes for more precise gene-editing

The CRISPR gene-editing tool may be one of the most important medical breakthroughs in decades, but there's still plenty of room for improvement. Although Cas9 has been the go-to enzyme for gene-editing, that doesn't mean it's necessarily the best option. Now a team of scientists, including the co-creator of CRISPR, has engineered a more precise enzyme, known as Cas12b.
CRISPR works on the genome like a pair of scissors, allowing scientists to target specific DNA sequences – say, those that raise your chances of certain diseases – then snip them out and replace them with more beneficial genes. The enzyme Cas9 has traditionally done the heavy lifting, by binding to the target and performing the required edits.
But it's not flawless. Concerns have been raised in the past that Cas9 isn't picky enough, with the potential to cause unintended mutations in other parts of the genome, and may increase a patient's cancer risk. Although some studies pointing out these problems were later retracted, it's still not a bad idea to investigate alternatives in case safer options are out there.
And Cas12b might just fit the bill. The researchers say the new enzyme is smaller and can home in on targets more precisely than Cas9, and they demonstrated its prowess by editing primary human T cells. As the foot soldiers of the immune system, fine-tuning these cells could improve a whole range of immunotherapy treatments.
"This is further evidence that there are many useful CRISPR systems waiting to be discovered," says Jonathan Strecker, first author of the study.
Although Cas12b was identified as a CRISPR candidate as far back as 2015, it wasn't easy to get it up to scratch. This enzyme is sourced from bacteria that prefer hot environments like volcanoes and deep sea hydrothermal vents, so it operates at temperatures higher than the human body. To find a version that could work under cooler conditions, the team scanned the genetic sequences of thousands of bacteria, eventually settling on one found in a bug called Bacillus hisashii.
To speed up progress, the researchers have freely opened up the CRISPR-Cas12b system to academic teams everywhere.
The research was published in the journal Nature Communications.
Source: MIT

关键词:基因编辑技术