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

23 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)
Pages (from-to)	1266-1273
Number of pages	8
Journal	Nature Biotechnology
Volume	43
Issue number	8
DOIs	https://doi.org/10.1038/s41587-024-02422-w
State	Published - Aug 2025

All Science Journal Classification (ASJC) codes

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Biomedical Engineering
Molecular Medicine

Access to Document

10.1038/s41587-024-02422-w

Cite this

@article{00fa8eed5fd84a878ef900f042c5226e,

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

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.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.",

year = "2025",

month = aug,

doi = "10.1038/s41587-024-02422-w",

language = "English (US)",

volume = "43",

pages = "1266--1273",

journal = "Nature Biotechnology",

issn = "1087-0156",

publisher = "Nature Research",

number = "8",

}

TY - JOUR

T1 - Model-directed generation of artificial CRISPR–Cas13a guide RNA sequences improves nucleic acid detection

AU - Mantena, Sreekar

AU - Pillai, Priya P.

AU - Petros, Brittany A.

AU - Welch, Nicole L.

AU - Myhrvold, Cameron

AU - Sabeti, Pardis C.

AU - Metsky, Hayden C.

N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

PY - 2025/8

Y1 - 2025/8

N2 - 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.

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.

UR - https://www.scopus.com/pages/publications/85206626859

UR - https://www.scopus.com/pages/publications/85206626859#tab=citedBy

U2 - 10.1038/s41587-024-02422-w

DO - 10.1038/s41587-024-02422-w

M3 - Article

C2 - 39394482

AN - SCOPUS:85206626859

SN - 1087-0156

VL - 43

SP - 1266

EP - 1273

JO - Nature Biotechnology

JF - Nature Biotechnology

IS - 8

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this