CRISPR-induced DNA reorganization for multiplexed nucleic acid detection.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
17 03 2023
Historique:
received: 28 01 2022
accepted: 17 02 2023
entrez: 18 3 2023
pubmed: 19 3 2023
medline: 22 3 2023
Statut: epublish

Résumé

Nucleic acid sensing powered by the sequence recognition of CRIPSR technologies has enabled major advancement toward rapid, accurate and deployable diagnostics. While exciting, there are still many challenges facing their practical implementation, such as the widespread need for a PAM sequence in the targeted nucleic acid, labile RNA inputs, and limited multiplexing. Here we report FACT (Functionalized Amplification CRISPR Tracing), a CRISPR-based nucleic acid barcoding technology compatible with Cas12a and Cas13a, enabling diagnostic outputs based on cis- and trans-cleavage from any sequence. Furthermore, we link the activation of CRISPR-Cas12a to the expression of proteins through a Reprogrammable PAIRing system (RePAIR). We then combine FACT and RePAIR to create FACTOR (FACT on RePAIR), a CRISPR-based diagnostic, that we use to detect infectious disease in an agricultural use case: honey bee viral infection. With high specificity and accuracy, we demonstrate the potential of FACTOR to be applied to the sensing of any nucleic acid of interest.

Identifiants

pubmed: 36932065
doi: 10.1038/s41467-023-36874-6
pii: 10.1038/s41467-023-36874-6
pmc: PMC10022571
doi:

Substances chimiques

DNA 9007-49-2
Nucleic Acids 0
RNA 63231-63-0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1505

Informations de copyright

© 2023. The Author(s).

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Auteurs

Margot Karlikow (M)

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada. margot.karlikow@gmail.com.

Evan Amalfitano (E)

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.

Xiaolong Yang (X)

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.

Jennifer Doucet (J)

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.

Abigail Chapman (A)

Department of Biochemistry & Molecular Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.

Peivand Sadat Mousavi (PS)

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.

Paige Homme (P)

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.

Polina Sutyrina (P)

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.

Winston Chan (W)

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.

Sofia Lemak (S)

Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, M5S 3E5, Canada.

Alexander F Yakunin (AF)

Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, M5S 3E5, Canada.
Centre for Environmental Biotechnology, School of Natural Sciences, Bangor University, Bangor, Gwynedd, LL57 2UW, UK.

Adam G Dolezal (AG)

Department of Entomology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.

Shana Kelley (S)

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.
Institute of Biomedical Engineering, University of Toronto, Toronto, ON, M5S 3G9, Canada.
Department of Chemistry, Faculty of Arts and Science, University of Toronto, Toronto, ON, M5S 3H4, Canada.
Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, IL, 60611, USA.
Department of Chemistry, Northwestern University, Evanston, IL, 60208, USA.
Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA.

Leonard J Foster (LJ)

Department of Biochemistry & Molecular Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.

Brock A Harpur (BA)

Department of Entomology, Purdue University, 901 W State Street, West Lafayette, IN, 47907, USA.

Keith Pardee (K)

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada. keith.pardee@utoronto.ca.
Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, M5S 1A1, Canada. keith.pardee@utoronto.ca.

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Classifications MeSH