由人工智能指导的Cas9工程提供了一种有效的策略,以增强基础编辑
Dongyi Wei1, Peng Cheng2, Ziguo Song3
1Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Molecular systems biology
|September 15, 2025
概括
人工智能 (AI) 模型增强了基因编辑工具. 这项研究使用人工智能设计了一种Cas9变体 (AncBE4max-AI-8.3),编辑效率提高了2-3倍,改进了各种基础编辑器.
科学领域:
- 分子生物学分子生物学
- 生物工程是生物工程.
- 遗传学 是一个遗传学.
背景情况:
- 精确的基因组编辑对于生物研究和治疗应用至关重要.
- 当前的基础编辑器需要优化以提高其编辑效率.
- 蛋白质设计和人工智能的进步使复杂的蛋白质工程成为可能.
研究的目的:
- 使用人工智能驱动的蛋白质工程来优化基层编辑器的效率.
- 开发一个具有增强编辑能力的高性能Cas9变体.
- 验证人工智能引导的策略对改进基因编辑工具的普遍适用性.
主要方法:
- 利用蛋白质突变效应预测器 (ProMEP) 预测Cas9.9的单位突变.
- 在AncBE4max基编辑器原型中设计和测试了18点突变.
- 预测并结合多个突变来创建一个优化的变体,AncBE4max-AI-8.3.3.
主要成果:
- 开发了AncBE4max-AI-8.3变体,显示平均编辑效率增加了2-3倍.
- 成功提高了多个基础编辑器的性能,包括CGBE,YEE-BE4max,ABE-max,ABE-8e和HF-BEs.
- 在7个癌细胞系和人类胚胎干细胞中观察到编辑效率的稳定增强.
结论:
- 人工智能模型是基因编辑的背景下蛋白质工程的有效工具.
- 开发的人工智能引导策略提供了一种通用方法,以提高各种基因编辑工具的效率.
- 工程基础编辑器在各种蜂环境中显示了广泛的适用性和稳定的性能.
相关概念视频
CRISPR/Cas9 Genome Editing
1.7K
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...
1.7K
CRISPR
57.5K
Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
57.5K
Homologous Recombination
62.7K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
62.7K
CRISPR and crRNAs
18.7K
Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
18.7K
Conservative Site-specific Recombination and Phase Variation
6.7K
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...
6.7K


