Structural basis for the activation of a compact CRISPR-Cas13 nuclease

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dc.citation.articleNumber5845en_US
dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber14en_US
dc.contributor.authorDeng, Xiangyuen_US
dc.contributor.authorOsikpa, Emmanuelen_US
dc.contributor.authorYang, Jieen_US
dc.contributor.authorOladeji, Seye J.en_US
dc.contributor.authorSmith, Jamieen_US
dc.contributor.authorGao, Xueen_US
dc.contributor.authorGao, Yangen_US
dc.date.accessioned2024-05-03T15:51:18Zen_US
dc.date.available2024-05-03T15:51:18Zen_US
dc.date.issued2023en_US
dc.description.abstractThe CRISPR-Cas13 ribonucleases have been widely applied for RNA knockdown and transcriptional modulation owing to their high programmability and specificity. However, the large size of Cas13 effectors and their non-specific RNA cleavage upon target activation limit the adeno-associated virus based delivery of Cas13 systems for therapeutic applications. Herein, we report detailed biochemical and structural characterizations of a compact Cas13 (Cas13bt3) suitable for adeno-associated virus delivery. Distinct from many other Cas13 systems, Cas13bt3 cleaves the target and other nonspecific RNA at internal “UC” sites and is activated in a target length-dependent manner. The cryo-electron microscope structure of Cas13bt3 in a fully active state illustrates the structural basis of Cas13bt3 activation. Guided by the structure, we obtain engineered Cas13bt3 variants with minimal off-target cleavage yet maintained target cleavage activities. In conclusion, our biochemical and structural data illustrate a distinct mechanism for Cas13bt3 activation and guide the engineering of Cas13bt3 applications.en_US
dc.identifier.citationDeng, X., Osikpa, E., Yang, J., Oladeji, S. J., Smith, J., Gao, X., & Gao, Y. (2023). Structural basis for the activation of a compact CRISPR-Cas13 nuclease. Nature Communications, 14(1), 5845. https://doi.org/10.1038/s41467-023-41501-5en_US
dc.identifier.digitals41467-023-41501-5en_US
dc.identifier.doihttps://doi.org/10.1038/s41467-023-41501-5en_US
dc.identifier.urihttps://hdl.handle.net/1911/115610en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleStructural basis for the activation of a compact CRISPR-Cas13 nucleaseen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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