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

ABSTRACT: 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.

SUBMITTER: Mantena S

PROVIDER: S-EPMC10541601 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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

Mantena Sreekar S Pillai Priya P PP Petros Brittany A BA Welch Nicole L NL Myhrvold Cameron C Sabeti Pardis C PC Metsky Hayden C HC

bioRxiv : the preprint server for biology 20230920

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 pathog ...[more]

PMID: 37786711

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