设计的Un1Cas12f1用于多重基因组编辑,具有增强的活动和准范围
Yanan Huo1, Jiale Mei1, Dan Zhang1
1Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Nature communications
|February 18, 2026
概括
工程CRISPR-Cas12f (evoCas12f) 扩展了PAM识别并提高了基因编辑效率. 这种优化的系统可以实现精确的基因组工程,包括小鼠的同卵性突变,从而推进治疗应用.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物技术是生物技术.
背景情况:
- 克里斯普尔-Cas12f系统显示出AAV传递基因疗法的前景.
- 它的使用受到狭窄的PAM识别 (TTTR) 和较低的编辑效率的限制.
研究的目的:
- 设计一个优化的CRISPR-Cas12f变体,具有扩展的PAM识别和改进的编辑效率.
- 为了证明工程变异对各种基因组工程应用的实用性.
主要方法:
- 细菌图书馆查被用于识别有益突变.
- 哺乳动物细胞验证证实了工程变异的性能.
- 该系统适应了转录激活和基编辑.
主要成果:
- 工程设计的evoCas12f变种展示了扩展到NTNR/NYTR的PAM识别.
- 它显示TTTR站点的活动增长了1.4倍,编辑效率高达91%.
- 在F0小鼠中,即使在非正规的PAM位点,也能有效地产生同卵性突变.
结论:
- evoCas12f是一个紧的,高效的CRISPR平台.
- 它可以实现多重编辑和高分辨率定位.
- 这一进步扩大了治疗基因组工程的可能性.
更多相关视频
相关概念视频
01:28CRISPR/Cas9 Genome Editing
2.1K
The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...
2.1K
02:53Conservative Site-specific Recombination and Phase Variation
6.9K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.9K