The use of genetically modified animals for human diseases contributes to the understanding of the pathogenesis of various diseases and aids in the search for effective treatments. Consequently, there is an emerging trend of establishing appropriate genetic animal models capable of recapitulating the crucial phenotypes of human diseases to facilitate investigations about the pathogenesis and effective treatments. Recently, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas) technology demonstrated its successful application in genetically modifying the genomes of diverse species. Furthermore, CRISPR/ Cas technology has been established as a tool for producing genetic animal models that more faithfully mimic human diseases. In this review, we have focused on the application of CRISPR/Cas technology in developing innovative genetic animal models for the study of human diseases, specifically for the investigation of disease pathogenesis and treatment. We have also discussed the current technical challenges of CRISPR technology, such as off-target effects, and reviewed the emerging strategies developed to enhance its precision. Finally, we have provided an overview of the considerable potential of advanced tools derived from the CRISPR/dead Cas9 (dCas9) system, such as base and prime editors, and explore their future applications in creating more sophisticated disease models.

ABSTRACT
INTRODUCTION
CRISPR/CAS9 SYSTEM AND THEAPPLICATION OF GENETIC EDITING
METHOD FOR ESTABLISHING ANIMALMODELS USING THE CRISPR/CAS9 SYSTEM
    Somatic cell nuclear transfer (SCNT)
    Microinjection
    Electroporation
ESTABLISHING ANIMAL MODELS OF HUMANDISEASE VIA GENOME EDITING USING THECRISPR/CAS9 SYSTEM
    Small animal models (mice and rats)
    Large animal models (rabbit, dog, and pig)
    Nonhuman primate models
CONCLUSION
REFERENCES

• Boyoung Kim(Laboratory of Molecular Genetics, College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea)
• Hanseul Park(Laboratory of Molecular Genetics, College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea) Corresponding author
• Seongju Lee(Laboratory of Theriogenology and Reproductive Biotechnology, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Korea)
• Yubyeol Jeon(Laboratory of Theriogenology and Reproductive Biotechnology, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea)