Model-directed Generation of Artificial CRISPR-Cas13a Guide RNA Sequences Improves Nucleic Acid Detection.

Details

• Alternative Title:
  Nature Biotechnology, 2025, v. 43, no. 8: Model-directed Generation of Artificial CRISPR-Cas13a Guide RNA Sequences Improves Nucleic Acid Detection.
• Journal Article:
  Nature Biotechnology
• Personal Author:
  Mantena, Sreekar ; Pillai, Priya P. ; Petros, Brittany A. ; Welch, Nicole L. ; Myhrvold, Cameron ; Sabeti, Pardis C. ; Metsky, Hayden C.
• Description:
  CRISPR guide RNA sequences deriving exactly from natural sequences may not perform optimally in every application. Here we implement and evaluate algorithms for designing maximally fit, artificial CRISPR-Cas13a guides with multiple mismatches to natural sequences that are tailored for diagnostic applications. These guides offer more sensitive detection of diverse pathogens and discrimination of pathogen variants compared with guides derived directly from natural sequences and illuminate design principles that broaden Cas13a targeting.
• Content Notes:
  Author manuscript
• Subjects:
  • CRISPR-Cas Systems
  • RNA, Guide, CRISPR-Cas Systems
  • Algorithms
  • Base Sequence
  • Clustered Regularly Interspaced Short Palindromic Repeats
• Source:
  Nature Biotechnology, 2025, v. 43, no. 8
• DOI:
  https://doi.org/10.1038/s41587-024-02422-w
• ISSN:
  1087-0156 ; 1546-1696
• Pubmed ID:
  39394482
• Pubmed Central ID:
  PMC12439118
• Document Type:
  Text
• Funding:
  T32 GM007753/GM/NIGMS NIH HHSUnited States/ ; T32 GM144273/GM/NIGMS NIH HHSUnited States/ ; T32GM007753/U.S. Department of Health & Human Services ; NIH ; National Institute of General Medical Sciences (NIGMS)/ ; INV-034761/GATES/Gates FoundationUnited States/ ; T32GM144273/U.S. Department of Health & Human Services ; NIH ; National Institute of General Medical Sciences (NIGMS)/ ; K01 AI163498/AI/NIAID NIH HHSUnited States/ ; U01AI151812/Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; D18AC00006/United States Department of Defense ; Defense Advanced Research Projects Agency (DARPA)/ ; 75D30122C15113/U.S. Department of Health & Human Services ; Centers for Disease Control and Prevention (CDC)/ ; K01AI163498/U.S. Department of Health & Human Services ; NIH ; National Institute of Allergy and Infectious Diseases (NIAID)/ ; NU50CK000629/U.S. Department of Health & Human Services ; Centers for Disease Control and Prevention (CDC)/ ; U01 AI151812/AI/NIAID NIH HHSUnited States/ ; U19 AI110818/AI/NIAID NIH HHSUnited States/ ; INV-034761/GATES/Gates FoundationUnited States/ ; U19AI110818/Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/
• Genre:
  Journal Article
• Pages in Document:
  1266-1273 (28 pdf pages)
• Volume:
  43
• Issue:
  8
• Download URL:
  https://stacks.cdc.gov/view/cdc/261988/cdc_261988_DS1.pdf
• File Type:
  [PDF - 1.61 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:f10bc697b4615b8a6ea468b2a8d9704d2a89eaa31623f6073c12d12659624ce4fed27a65e52900b450b82703cf01d9bbd276025f995b1307cadbaf5909e14543