Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder leading to beta-cell destruction and absolute insulin 
deficiency, necessitating lifelong insulin therapy. While insulin therapy remains the standard for glycaemic control, 
it does not address the underlying autoimmune pathology or restore endogenous insulin production. This review 
compared the effect of CRISPR-Cas9-mediated beta-cell editing with standard insulin therapy on glycaemic control 
in adults with type 1 diabetes. A narrative review approach was utilised to synthesise published evidence on 
mechanisms, efficacy, safety, translational feasibility, and ethical considerations of CRISPR-Cas9 beta-cell editing 
versus insulin therapy. Insulin therapy effectively reduced hyperglycaemia and prevents acute complications, but 
carries limitations such as hypoglycaemia risk, imperfect glycaemic control, and inability to replicate physiological 
insulin secretion. Conversely, CRISPR-Cas9 beta-cell editing demonstrates promise in preclinical studies, enabling 
restoration of insulin production through edited stem-cell-derived beta-like cells or immune modulation to prevent 
beta-cell destruction. Such editing offers potential durable remission or cure of T1DM. However, clinical translation 
is limited by challenges in delivery systems, off-target effects, immunogenicity, regulatory approvals, and ethical 
concerns. No human clinical trial data currently exist to validate safety and efficacy. CRISPR-Cas9 beta-cell editing 
offers a potential disease-modifying alternative to insulin therapy for type 1 diabetes, though significant translational 
research is required before clinical adoption. Integrating gene editing with existing insulin management may 
optimise future therapeutic strategies for durable glycaemic control and improved patient outcomes. 
Keywords: CRISPR-Cas9 beta-cell editing, Type 1 diabetes mellitus, Insulin therapy, Glycaemic control, Gene 
editing therapy.