Emerging role of gene therapy in immune modulation and beta-cell preservation in Type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease characterised by the destruction of insulin-producing β cells, which leads to chronic hyperglycaemia and lifelong insulin dependence. Despite advances in diabetes care, achieving optimal glucose control and preventing complications remains a challenge. Gene therapy has emerged as a transformative approach, targeting the underlying mechanisms of β-cell destruction and immune dysregulation. Studies have suggested the feasibility of using viral vectors, such as adeno-associated viruses (AAVs) and lentiviruses, to deliver genes aimed at preserving pancreatic function and restoring immune balance. Innovative strategies, including CRISPR/Cas9-based genome editing and non-viral delivery systems, offer promise for addressing safety and efficacy challenges. This systematic review aims to evaluate the current state of gene therapy in T1D, focusing on findings from preclinical studies and ongoing clinical trials. It explores key approaches, such as β-cell regeneration, immune tolerance induction, and metabolic regulation, while critically assessing challenges related to delivery efficiency, long-term effects, and scalability. By synthesising existing evidence, this review provides a comprehensive overview of the progress and obstacles in translating gene therapy into a viable treatment for T1D, highlighting future directions to accelerate clinical application.