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

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

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引用次数: 0

摘要

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。

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

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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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

期刊介绍： Nature Biotechnology is a monthly journal that focuses on the science and business of biotechnology. It covers a wide range of topics including technology/methodology advancements in the biological, biomedical, agricultural, and environmental sciences. The journal also explores the commercial, political, ethical, legal, and societal aspects of this research. The journal serves researchers by providing peer-reviewed research papers in the field of biotechnology. It also serves the business community by delivering news about research developments. This approach ensures that both the scientific and business communities are well-informed and able to stay up-to-date on the latest advancements and opportunities in the field. Some key areas of interest in which the journal actively seeks research papers include molecular engineering of nucleic acids and proteins, molecular therapy, large-scale biology, computational biology, regenerative medicine, imaging technology, analytical biotechnology, applied immunology, food and agricultural biotechnology, and environmental biotechnology. In summary, Nature Biotechnology is a comprehensive journal that covers both the scientific and business aspects of biotechnology. It strives to provide researchers with valuable research papers and news while also delivering important scientific advancements to the business community.