Model-directed generation of CRISPR-Cas13a guide RNAs designs artificial sequences that improve nucleic acid detection

Generating maximally-fit biological sequences has the potential to transform CRISPR guide RNA design as it has other areas of biomedicine. Here, we introduce model-directed exploration algorithms (MEAs) for designing maximally-fit, artificial CRISPR-Cas13a guides—with multiple mismatches to any natu...

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Autores principales: Mantena, Sreekar, Pillai, Priya P., Petros, Brittany A., Welch, Nicole L., Myhrvold, Cameron, Sabeti, Pardis C., Metsky, Hayden C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541601/
https://www.ncbi.nlm.nih.gov/pubmed/37786711
http://dx.doi.org/10.1101/2023.09.20.557569
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author Mantena, Sreekar
Pillai, Priya P.
Petros, Brittany A.
Welch, Nicole L.
Myhrvold, Cameron
Sabeti, Pardis C.
Metsky, Hayden C.
author_facet Mantena, Sreekar
Pillai, Priya P.
Petros, Brittany A.
Welch, Nicole L.
Myhrvold, Cameron
Sabeti, Pardis C.
Metsky, Hayden C.
author_sort Mantena, Sreekar
collection PubMed
description Generating maximally-fit biological sequences has the potential to transform CRISPR guide RNA design as it has other areas of biomedicine. Here, we introduce model-directed exploration algorithms (MEAs) for designing maximally-fit, artificial CRISPR-Cas13a guides—with multiple mismatches to any natural sequence—that are tailored for desired properties around nucleic acid diagnostics. We find that MEA-designed guides offer more sensitive detection of diverse pathogens and discrimination of pathogen variants compared to guides derived directly from natural sequences, and illuminate interpretable design principles that broaden Cas13a targeting.
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spelling pubmed-105416012023-10-02 Model-directed generation of CRISPR-Cas13a guide RNAs designs artificial sequences that improve nucleic acid detection Mantena, Sreekar Pillai, Priya P. Petros, Brittany A. Welch, Nicole L. Myhrvold, Cameron Sabeti, Pardis C. Metsky, Hayden C. bioRxiv Article Generating maximally-fit biological sequences has the potential to transform CRISPR guide RNA design as it has other areas of biomedicine. Here, we introduce model-directed exploration algorithms (MEAs) for designing maximally-fit, artificial CRISPR-Cas13a guides—with multiple mismatches to any natural sequence—that are tailored for desired properties around nucleic acid diagnostics. We find that MEA-designed guides offer more sensitive detection of diverse pathogens and discrimination of pathogen variants compared to guides derived directly from natural sequences, and illuminate interpretable design principles that broaden Cas13a targeting. Cold Spring Harbor Laboratory 2023-09-20 /pmc/articles/PMC10541601/ /pubmed/37786711 http://dx.doi.org/10.1101/2023.09.20.557569 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Mantena, Sreekar
Pillai, Priya P.
Petros, Brittany A.
Welch, Nicole L.
Myhrvold, Cameron
Sabeti, Pardis C.
Metsky, Hayden C.
Model-directed generation of CRISPR-Cas13a guide RNAs designs artificial sequences that improve nucleic acid detection
title Model-directed generation of CRISPR-Cas13a guide RNAs designs artificial sequences that improve nucleic acid detection
title_full Model-directed generation of CRISPR-Cas13a guide RNAs designs artificial sequences that improve nucleic acid detection
title_fullStr Model-directed generation of CRISPR-Cas13a guide RNAs designs artificial sequences that improve nucleic acid detection
title_full_unstemmed Model-directed generation of CRISPR-Cas13a guide RNAs designs artificial sequences that improve nucleic acid detection
title_short Model-directed generation of CRISPR-Cas13a guide RNAs designs artificial sequences that improve nucleic acid detection
title_sort model-directed generation of crispr-cas13a guide rnas designs artificial sequences that improve nucleic acid detection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541601/
https://www.ncbi.nlm.nih.gov/pubmed/37786711
http://dx.doi.org/10.1101/2023.09.20.557569
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