Precise genome-editing in human diseases:mechanisms,strategies and applications

Precise genome-editing platforms are versatile tools for generating specific,site-directed DNA insertions,deletions,and substitutions.The continuous enhancement of these tools has led to a revolution in the life sciences,which promises to deliver novel therapies for genetic disease.Precise genome-editing can be traced back to the 1950s with the discovery of DNA’s doublehelix and,after 70 years of development,has evolved from crude in vitro applications to a wide range of sophisticated capabilities,including in vivo applications.Nonetheless,precise genome-editing faces constraints such as modest efficiency,delivery challenges,and off-target effects.In this review,we explore precise genome-editing,with a focus on introduction of the landmark events in its history,various platforms,delivery systems,and applications.First,we discuss the landmark events in the history of precise genome-editing.Second,we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human genome.Third,we introduce the current delivery systems used to deploy precise genome-editing components through DNA,RNA,and RNPs.Finally,we summarize the current applications of precise genome-editing in labeling endogenous genes,screening genetic variants,molecular recording,generating disease models,and gene therapy,including ex vivo therapy and in vivo therapy,and discuss potential future advances.