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.

中文翻译：

---

人工 CRISPR-Cas13a 向导 RNA 序列的模型定向生成改善了核酸检测

完全源自天然序列的 CRISPR 向导 RNA 序列可能无法在每个应用中都发挥最佳性能。在这里，我们实施并评估了用于设计最大拟合的人工 CRISPR-Cas13a 指南的算法，这些指南与为诊断应用量身定制的自然序列具有多个不匹配。与直接来自自然序列的指南相比，这些指南可以更灵敏地检测各种病原体和区分病原体变异，并阐明拓宽 Cas13a 靶向的设计原则。