Abstract

Monogenic diabetes represents approximately 1-5% of all diabetes cases globally, with mutations in over 40 genes 
causing various forms of maturity onset diabetes of the young (MODY) and neonatal diabetes mellitus. The 
emergence of clustered regularly interspaced short palindromic repeats (CRISPR) technology has revolutionized 
therapeutic approaches for genetic disorders, offering unprecedented precision in correcting disease-causing 
mutations. This review examined the current state of CRISPR based gene editing applications for monogenic 
diabetes, analyzing therapeutic strategies, molecular mechanisms, and clinical translation challenges. A 
comprehensive literature search was conducted using PubMed and Web of Science databases from 2012-2025, 
focusing on peer reviewed articles describing CRISPR applications in monogenic diabetes models and clinical 
studies. Recent advances demonstrated successful correction of pathogenic variants in HNF1A, HNF4A, INS, and 
KCNJ11 genes using base editing and prime editing technologies, with correction efficiencies ranging from 15-85% 
in cellular models. Clinical applications showed promise for treating MODY subtypes, with patient derived induced 
pluripotent stem cells (iPSCs) serving as valuable platforms for personalized therapy development. Current 
limitations include delivery challenges, off target effects, and regulatory considerations for germline editing. 
CRISPR based approaches represent a paradigm shift toward precision medicine for monogenic diabetes, with base 
editing and prime editing emerging as safer alternatives to traditional nuclease-based systems for therapeutic 
applications. 
Keywords: CRISPR gene editing, Monogenic diabetes, Precision medicine, Base editing, Prime editing