Model-directed generation of artificial CRISPR–Cas13a guide RNA sequences improves nucleic acid detection

Sreekar Mantena; Priya P. Pillai; Brittany A. Petros; Nicole L. Welch; Cameron Myhrvold; Pardis C. Sabeti; Hayden C. Metsky

doi:10.1038/s41587-024-02422-w

Model-directed generation of artificial CRISPR–Cas13a guide RNA sequences improves nucleic acid detection

Sreekar Mantena, Priya P. Pillai, Brittany A. Petros, Nicole L. Welch, Cameron Myhrvold, Pardis C. Sabeti, Hayden C. Metsky

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

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.

Original language	English (US)
Journal	Nature biotechnology
DOIs	https://doi.org/10.1038/s41587-024-02422-w
State	Accepted/In press - 2024

All Science Journal Classification (ASJC) codes

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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10.1038/s41587-024-02422-w

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abstract = "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.",

author = "Sreekar Mantena and Pillai, {Priya P.} and Petros, {Brittany A.} and Welch, {Nicole L.} and Cameron Myhrvold and Sabeti, {Pardis C.} and Metsky, {Hayden C.}",

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AU - Pillai, Priya P.

AU - Petros, Brittany A.

AU - Welch, Nicole L.

AU - Myhrvold, Cameron

AU - Sabeti, Pardis C.

AU - Metsky, Hayden C.

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AB - 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.

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JF - Nature biotechnology

ER -

Model-directed generation of artificial CRISPR–Cas13a guide RNA sequences improves nucleic acid detection

Abstract

All Science Journal Classification (ASJC) codes

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