相关实验视频

Updated: Jun 1, 2025

DNA Virus Detection System Based on RPA-CRISPR/Cas12a-SPM and Deep Learning

DNA Virus Detection System Based on RPA-CRISPR/Cas12a-SPM and Deep Learning

Published on: May 10, 2024

工程CRISPR-Cas PAM识别使用深度学习的巨大进化数据的工程

Stephen Nayfach¹, Aadyot Bhatnagar¹, Andrey Novichkov¹

¹Profluent Bio, Berkeley, CA, USA.

bioRxiv : the preprint server for biology

|January 20, 2025

概括

Protein2PAM是一个深度学习模型,准确地预测了CRISPR-Cas PAM的特异性,并为个性化基因组编辑设计了Cas酶. 这通过启用定制PAM识别来推进基因编辑.

科学领域:

生物技术是生物技术.
基因组学就是基因组学.
分子生物学分子生物学

背景情况:

对于基因组向,CRISPR-Cas酶需要对原体空间邻动机 (PAM) 的识别.
PAM的特异性限制了CRISPR-Cas系统可以编辑的序列范围.
蛋白质工程提供了一条定制Cas酶用于新型PAM识别的途径.

研究的目的:

开发一个人工智能驱动的工具,Protein2PAM,用于预测Cas蛋白PAM特异性.
使用Protein2PAM来设计具有改变PAM识别能力的Cas酶.
展示机器学习在定制CRISPR-Cas系统中的应用,用于基因组编辑.

主要方法:

开发了Protein2PAM,这是一个以进化为基础的深度学习模型,在超过45,000个CRISPR-Cas PAM序列上训练.
应用了深度突变扫描以识别PAM识别的关键残留物在Cas9.
使用Protein2PAM扩大PAM识别的Nme1Cas9变体的计算进化.

主要成果:

Protein2PAM准确地预测了在I型,II型和V型CRISPR-Cas系统中的PAM特异性.
在Cas9中识别了PAM识别的关键残留物,而不依赖结构数据.
产生的Nme1Cas9变体具有扩展的PAM识别和高达50倍的分裂率in vitro.

结论:

Protein2PAM是机器学习的第一个成功应用,用于定制Cas酶PAM识别.
这种方法可以为特定的个性化基因组编辑应用程序设计Cas酶.
这些发现为使用CRISPR-Cas技术进行更广泛,更精确的基因组向铺平了道路.

关键词:

这就是CRISPR-Cas.深度学习是一种深度学习.基因组编辑基因组编辑蛋白质设计蛋白质设计

更多相关视频

Using Sniper-Cas9 to Minimize Off-target Effects of CRISPR-Cas9 Without the Loss of On-target Activity Via Directed Evolution

Using Sniper-Cas9 to Minimize Off-target Effects of CRISPR-Cas9 Without the Loss of On-target Activity Via Directed Evolution

Published on: February 26, 2019

Gene Digital Circuits Based on CRISPR-Cas Systems and Anti-CRISPR Proteins

Gene Digital Circuits Based on CRISPR-Cas Systems and Anti-CRISPR Proteins

Published on: October 18, 2022

相关概念视频

CRISPR

CRISPR

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...

CRISPR and crRNAs

CRISPR and crRNAs

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...

Homologous Recombination

Homologous Recombination

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...