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

IF 33.1 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Nature biotechnology Pub Date : 2024-10-11 DOI:10.1038/s41587-024-02422-w

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

引用次数: 0

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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以模型为导向生成人工 CRISPR-Cas13a 引导 RNA 序列，提高核酸检测能力

完全源自天然序列的 CRISPR 引导 RNA 序列可能无法在每种应用中都发挥最佳性能。在这里，我们实现并评估了设计最大拟合人工 CRISPR-Cas13a 引导序列的算法，这些引导序列与天然序列有多个错配，是为诊断应用量身定制的。与直接从天然序列中提取的引导物相比，这些引导物能更灵敏地检测各种病原体并区分病原体变体，同时还阐明了扩大Cas13a靶向范围的设计原则。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature biotechnology 工程技术-生物工程与应用微生物

CiteScore

63.00

自引率

1.70%

发文量

382

审稿时长

3 months

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