CRISPR-Cas9 Genome Editing as a Potential Therapeutic Approach for Type 1 Diabetes Mellitus: A Translational Review

Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by the immunemediated destruction of pancreatic β-cells, resulting in absolute insulin deficiency. Although current therapeutic strategies primarily focus on glycemic control, they fail to address the underlying autoimmune pathophysiology of the disease. In this context, CRISPR-Cas9 gene-editing technology has emerged as a promising approach to precisely modify disease-associated genes, restore endogenous β-cell function, and modulate immune tolerance. Importantly, the integration of CRISPR-based gene editing with cellular therapies, particularly induced pluripotent stem cell–derived β-cell replacement strategies, offers a synergistic framework to simultaneously overcome β-cell loss and immunemediated rejection. Preclinical studies in T1D mouse models have demonstrated that genetically engineered stem cell–derived β-cells, including those with targeted knockout of human leukocyte antigen class 1 and 2 molecules, can achieve long-term insulin secretion and reverse hyperglycemia without eliciting immune rejection. Despite these advances, challenges related to off-target effects, ethical considerations, and regulatory constraints remain significant barriers to clinical translation. Nevertheless, continued progress in CRISPR technologies, bioinformatics-guided editing strategies, and stem cell engineering may ultimately enable the development of durable and potentially curative therapeutic approaches for T1D. Cite this article as: Karataş MH, Eslamkhah S, Aslan ES. CRISPR-Cas9 genome editing as a potential therapeutic approach for type 1 diabetes mellitus: A translational review. Endocrinol Res Pract. 2026;30(2):120-126.