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相关概念视频

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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CRISPR01:59

CRISPR

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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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Language01:16

Language

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Language is a unique communication system that uses words and systematic rules to organize and transmit information. Unlike other forms of communication, which may involve postures, movements, odors, or vocalizations, language relies on symbols and grammar. This makes human communication distinct from that of other species, who also communicate but do not use language in the same way humans do.
Corballis and Suddendorf (2007) and Tomasello and Rakoczy (2003) highlight the role of language in...
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Components of Language01:24

Components of Language

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Language, whether spoken, signed, or written, consists of specific components: lexicon and grammar. The lexicon is the vocabulary of a language, comprising its words. Grammar is the set of rules used to convey meaning through the lexicon. For example, English grammar adds “-ed” to most verbs to indicate past tense. Words are formed by combining phonemes, which are the basic sound units of a language. Different languages have different sets of phonemes (e.g., “ah” vs.
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Language Development01:22

Language Development

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Children master language quickly and with relative ease, supported by both biological predisposition and reinforcement. B. F. Skinner (1957) proposed that language is learned through reinforcement, while Noam Chomsky (1965) argued that language acquisition mechanisms are biologically determined.
The critical period for language acquisition suggests that the ability to acquire language is at its peak early in life. As people age, this proficiency decreases. Language development begins very...
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Language and Cognition01:27

Language and Cognition

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Language serves as a bridge between ideas and communication, influencing how individuals perceive and interact with the world. Psychologists have long debated whether language shapes thought or vice versa. This discussion gained grip with Edward Sapir and Benjamin Lee Whorf in the 1940s, who proposed that language determines thought, a concept known as linguistic determinism. They suggested that the vocabulary and structure of a language influence how its speakers think and perceive reality.
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相关实验视频

Updated: Feb 4, 2026

Substrate Generation for Endonucleases of CRISPR/Cas Systems
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通过蛋白质语言模型定制CRISPR-Cas PAM特异性

Stephen Nayfach1, Aadyot Bhatnagar2, Andrey Novichkov2

  • 1Profluent Bio, Emeryville, CA, USA. snayfach@profluent.bio.

Nature biotechnology
|February 2, 2026
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概括

科学家们开发了Protein2PAM,这是一种深度学习模型,可以有效地为特定的DNA目标设计CRISPR-Cas变体. 这推动了基因组编辑的进步,克服了原空间体相邻的动图限制.

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Last Updated: Feb 4, 2026

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科学领域:

  • 基因编辑技术CRISPR-Cas是一种基因编辑技术.
  • 生物信息学和计算生物学
  • 蛋白质工程和定向进化研究

背景情况:

  • 克里斯普尔-卡斯系统需要原体空间相邻的基因 (PAM) 来定位DNA,限制可编辑基因组位点的范围.
  • 目前用于工程PAM特异性的方法往往是费力和耗时的,涉及代的实验步骤.

研究的目的:

  • 引入一个以进化为基础的深度学习模型,Protein2PAM,用于高效设计具有改变PAM特异性的Cas蛋白变体.
  • 通过克服CRISPR-Cas系统中的PAM约束来实现以前无法访问的基因组序列的精确准.

主要方法:

  • 在CRISPR-Cas PAM序列的大数据集 (>45,000) 上开发和训练了Protein2PAM.
  • 使用in silico mutagenesis来识别Cas9中PAM识别的关键残留物,而不依赖结构数据.
  • 使用Protein2PAM用于Nme1Cas9变体的计算进化.

主要成果:

  • 蛋白2PAM准确地预测了各种CRISPR-Cas类型 (I,II,V) 的PAM特异性.
  • 在Cas9中使用计算方法识别PAM识别的关键残留物.
  • 产生了Nme1Cas9变异,显著扩大了PAM识别,并且在体外裂解率增加了50倍.

结论:

  • Protein2PAM提供了一种高效的,以机器学习为驱动的方法,用于为特定的PAM识别设计CRISPR-Cas酶.
  • 这项技术扩大了CRISPR-Cas系统的准能力,提高了个性化基因组编辑应用程序的灵活性.