CRISPR Technologies in Type 2 Diabetes: From Mechanistic Insights to Therapeutic Discovery

Type 2 diabetes (T2D) is a complex metabolic disorder driven by the interplay of genetic susceptibility, β-cell dysfunction, and insulin resistance. Although genome-wide association studies (GWAS) have identified numerous T2D risk loci, translating these genetic findings into biological mechanisms and therapeutic strategies remains challenging. The emergence of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based technologies has provided powerful tools for precise genome manipulation and functional interrogation of disease-associated genes and genetic variations. This review summarizes the development of CRISPR technologies and highlights their applications in T2D research. We review the application of CRISPR technologies in T2D genetic factor analysis and high-throughput phenotypic screening, with a focus on three key areas: glucose metabolism, lipid metabolism, and pancreatic functionality. We further examine the role of CRISPR in therapeutics that target pancreatic β-cells via gene correction, stress protection, and epigenetic reprogramming. Finally, we briefly discuss the major challenges encountered in the applications of CRISPR technology, including delivery efficiency, off-target effects, safety concerns and ethical considerations.