计算机辅助CRISPR向导RNA设计

In silico CRISPR-based sgRNA design

摘要:

基于CRISPR/Cas9系统的基因编辑已被成功应用于多种细胞类型中。计算机辅助的向导RNA (Guide RNA) 设计是使用CRISPR系统成功进行基因编辑的关键步骤之一。目前的计算工作主要致力于利用计算模型来提高sgRNA的打靶效率并降低其脱靶。文中对于目前存在的sgRNA设计工具进行综述，并且说明可以通过建立高效的计算模型，对当前的异质基因编辑数据进行整合挖掘，以获得无偏差的sgRNA设计规则，并预测影响sgRNA设计的关键特征。笔者认为，对于sgRNA打靶和脱靶效果的系统总结和评价，将有助于使用CRISPR系统进行更加精准的基因编辑和基因治疗。

Abstract:

CRISPR-based genome editing has been widely implemented in various cell types. In-silico single guide RNA (sgRNA) design is a key step for successful gene editing using CRISPR system. Continuing efforts are made to refine in-silico sgRNA design with high on-target efficacy and reduced off-target effects. In this paper, we summarize the present sgRNA design tools, and show that efficient in-silico models can be built that integrate current heterogeneous genome-editing data to derive unbiased sgRNA design rules and identify key features for improving sgRNA design. Our review shows that systematic comparisons and evaluation of on-target and off-target effects of sgRNA will allow more precise genome editing and gene therapies using the CRISPR system.