Scholarlink

<p>CRISPR–Cas systems are transformative tools for gene editing that can be tuned or controlled by anti-CRISPRs (Acrs)—phage-derived inhibitors that regulate CRISPR–Cas activity. However, Acrs that can inhibit biotechnologically relevant CRISPR systems are relatively rare and challenging to discover. To overcome this limitation, we describe a highly successful and rapid approach that leverages de novo protein design to develop new-to-nature proteins for controlling CRISPR–Cas activity. Here, using <i>Leptotrichia</i> <i>buccalis</i> CRISPR–Cas13a as a representative example, we demonstrate that Acrs designed using artificial intelligence (AIcrs) are capable of highly potent and specific inhibition of CRISPR–Cas13a nuclease activity. We present a comprehensive workflow for design validation and demonstrate AIcr functionality in controlling CRISPR–Cas13 activity in bacterial and human cells. The ability to design bespoke inhibitors of Cas effectors will contribute to the ongoing development of CRISPR–Cas tools in diverse applications across research, medicine, agriculture and microbiology.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

De novo design of potent CRISPR–Cas13 inhibitors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月26日

查看全文
  • Cyntia Taveneau,
  • Her Xiang Chai,
  • Jovita D’Silva,
  • Rebecca S. Bamert,
  • Honglin Chen,
  • Brooke K. Hayes,
  • Roland W. Calvert,
  • Jacob Purcell,
  • Daniel J. Curwen,
  • Fabian Munder,
  • Lisandra L. Martin,
  • Jeremy J. Barr,
  • Joseph Rosenbluh,
  • Mohamed Fareh,
  • Rhys Grinter,
  • Gavin J. Knott

摘要

CRISPR–Cas systems are transformative tools for gene editing that can be tuned or controlled by anti-CRISPRs (Acrs)—phage-derived inhibitors that regulate CRISPR–Cas activity. However, Acrs that can inhibit biotechnologically relevant CRISPR systems are relatively rare and challenging to discover. To overcome this limitation, we describe a highly successful and rapid approach that leverages de novo protein design to develop new-to-nature proteins for controlling CRISPR–Cas activity. Here, using Leptotrichia buccalis CRISPR–Cas13a as a representative example, we demonstrate that Acrs designed using artificial intelligence (AIcrs) are capable of highly potent and specific inhibition of CRISPR–Cas13a nuclease activity. We present a comprehensive workflow for design validation and demonstrate AIcr functionality in controlling CRISPR–Cas13 activity in bacterial and human cells. The ability to design bespoke inhibitors of Cas effectors will contribute to the ongoing development of CRISPR–Cas tools in diverse applications across research, medicine, agriculture and microbiology.