The development of CRISPR-Cas9 technology has greatly promoted the progress of gene editing. Base editors and Prime editors developed based on this technology confer CRISPR-Cas9 system more powerful gene editing capabilities, and accelerate its application in clinical gene therapy. Although the CRISPR-Cas9 system has been optimized much, it still needs to be improved in terms of specificity, safety, and delivery in vivo. This review briefly introduces and looks forward to the research progress regarding the above three concerns.