Model-directed Generation of Artificial CRISPR-Cas13a Guide RNA Sequences Improves Nucleic Acid Detection

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2024 Oct 11

PMID 39394482

Authors

Sreekar Mantena

Priya P Pillai

Brittany A Petros

Nicole L Welch

Cameron Myhrvold

Pardis C Sabeti

Hayden C Metsky

Affiliations

Soon will be listed here.

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.

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RNA structure modulates Cas13 activity and enables mismatch detection.

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