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相关概念视频

CRISPR01:59

CRISPR

48.8K
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...
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CRISPR and crRNAs02:53

CRISPR and crRNAs

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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...
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Homologous Recombination02:31

Homologous Recombination

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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...
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A New Toolkit for Evaluating Gene Functions using Conditional Cas9 Stabilization
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CasGen:CRISPR Cas蛋白设计的规范化生成模型,具有分类和基于边际的优化.

Bharani Nammi1, Vindi M Jayasinghe-Arachchige2, Sita Sirisha Madugula2

  • 1Department of Industrial, Manufacturing and Systems Engineering, University of Texas at Arlington, Arlington, Texas, United States.

bioRxiv : the preprint server for biology
|March 10, 2025
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概括

CasGen,一个新的AI模型,设计了用于基因组编辑的新型聚类正规间隔短Palindromic重复 (CRISPR) 相关 (Cas) 蛋白质. 这扩大了合成生物学和治疗应用的工具包,具有精确和多功能Cas变体.

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科学领域:

  • 生物技术是生物技术.
  • 基因组学就是基因组学.
  • 蛋白质工程是指蛋白质工程.

背景情况:

  • 目前的基因组编辑依赖于一组有限的聚类定期间隔的短Palindromic重复 (CRISPR) 相关 (Cas) 蛋白质,主要是Cas9和Cas12变体.
  • 这种限制限制了基因组工程应用的范围和多功能性.

研究的目的:

  • 开发一种新的深度生成模型,CasGen,用于设计新的Cas9和Cas12蛋白质.
  • 为了提高产生的Cas蛋白质的质量和功能完整性,用于更广泛的基因组编辑应用.

主要方法:

  • 利用基于变压器的深度生成模型 (CasGen) 与基于边际的潜空间规范化.
  • 针对非Cas序列过的综合分类,用于指导设计的贝叶斯优化,以及基于AlphaFold的结构验证.
  • 编制了来自InterPro和PDB的3,021个Cas9,597个Cas12和597个非Cas蛋白序列的数据集.

主要成果:

  • 通过AlphaFold2/3.3.2,生成的Cas9和Cas12蛋白与已知的变体具有很高的结构相似性 (TM分数为0.70-0.85,RMSD<2.00 Å).
  • 序列身份分析揭示了新的Cas9基因 (28-55%的同一性) 和Cas12a变体 (多达48%的同一性).
  • BLAST 分析证实了生成的序列的新性,过了非常相似的现有 Cas 蛋白.

结论:

  • CasGen模型成功设计了多样化和功能健全的Cas蛋白质,显著扩大了基因组编辑工具包.
  • 这种深层次的生成方法对推进合成生物学和开发更精确,更通用的基于Cas的治疗工具具有前景.