Helicase-assisted continuous editing for programmable mutagenesis of endogenous genomes  

作　　者：Xi Dawn Chen 

机构地区：[1]不详

出　　处：《四川生理科学杂志》2024年第10期2326-2326,共1页

摘　　要：Deciphering the context-specific relationship between sequence and function is a major challenge in genomics.Existing tools for inducing locus-specific hypermutation and evolution in the native genome context are limited.Here we present a programmable platform for long-range,locus-specific hypermutation called helicase-assisted continuous editing(HACE).HACE leverages CRISPR-Cas9 to target a processive helicase-deaminase fusion that incurs mutations across large(>1000-base pair)genomic intervals.We applied HACE to identify mutations in mitogen-activated protein kinase kinase 1(MEK1)that confer kinase inhibitor resistance,to dissect the impact of individual variants in splicing factor 3B subunit 1(SF3B1)-dependent missplicing,and to evaluate noncoding variants in a stimulation-dependent immune enhancer of CD69.HACE provides a powerful tool for investigating coding and noncoding variants,uncovering combinatorial sequence-to-function relationships,and evolving new biological functions.

关 键 词：ENDOGENOUS STIMULATION CONTINUOUS 

分 类 号：Q78[生物学—分子生物学]