CRISPR-Cas9 Gene Editing for Monogenic Diabetes: Therapeutic Potential and Clinical Challenges
Zakaria Ali
Department of Pharmacy Kampala International University Uganda
Email: ali.zakaria@studwc.kiu.ac.ug
ABSTRACT
Monogenic diabetes mellitus comprised a heterogeneous group of disorders caused by single-gene mutations affecting pancreatic β-cell function or insulin action, accounting for approximately 1–2% of all diabetes cases yet frequently misdiagnosed as type 1 or type 2 diabetes. The advent of CRISPR-Cas9 gene editing technology had introduced unprecedented opportunities for definitive genetic correction of these conditions. This narrative review critically examined the therapeutic potential and translational challenges of CRISPR-Cas9 applications in monogenic diabetes. A comprehensive literature search was conducted using PubMed, Embase, and Web of Science databases (2015–2025) with terms including “CRISPR,” “gene editing,” “monogenic diabetes,” “MODY,” and “neonatal diabetes.” Principal findings reveal that CRISPR-Cas9 has demonstrated remarkable efficacy in correcting pathogenic mutations in patient-derived induced pluripotent stem cells and animal models of monogenic diabetes, with successful restoration of glucose-stimulated insulin secretion and normoglycemia. However, substantial barriers persisted including off-target mutagenesis, delivery vehicle limitations, immunogenicity concerns, and regulatory complexities that collectively impeded clinical translation. Emerging base editing and prime editing technologies offered enhanced precision with reduced double-strand breaks, potentially mitigating safety concerns. The evidence supported cautious optimism that CRISPR-based therapeutics may eventually provide curative interventions for monogenic diabetes, contingent upon resolution of safety, delivery, and ethical challenges through rigorous preclinical validation and carefully designed clinical trials.
Keywords: CRISPR-Cas9, Monogenic diabetes, Gene editing, MODY, Neonatal diabetes
CITE AS: Zakaria Ali (2026). CRISPR-Cas9 Gene Editing for Monogenic Diabetes: Therapeutic Potential and Clinical Challenges. IAA Journal of Scientific Research 13(1):1-11.