Emerging Biotechnological Approaches in Diabetes Mellitus: From Recombinant Insulin to Gene and Stem Cell Therapies

Biotechnology is revolutionizing the treatment of diabetes by shifting from glucose-lowering medications to therapeutic strategies. The most recent in vivo treatments and devices for diabetes are reviewed in this review. These include gene therapy (viral or nonviral delivery of insulin, glucokinase, growth factors, or immune-regulatory genes); cell therapy (allogeneic islet transplantation, stem cell-derived β cells, MSCs); immunomodulation (antibodies, Treg expansion, cytokine therapy to stop autoimmunity); bioengineering (encapsulation, scaffolds, and biomaterials to protect or regenerate β-cells); wearable artificial pancreas with sensors and pumps); CRISPR/genome editing (targeted correction of diabetes genes or microbiome). We outline the mechanisms of action for each, compile preclinical and clinical evidence of safety and efficacy, record trial results and regulatory status, Key findings include: AAV-mediated co-delivery of insulin and glucokinase genes achieved ~8-year normoglycemia in diabetic dogs. Islet transplants and stem cell therapies can restore insulin secretion, especially when combined with encapsulation. Teplizumab (anti-CD3) delayed T1D onset by ~33 months in high-risk subjects, but most immune therapies have only transient effects. Glucose-responsive “smart” patches and closed-loop pumps significantly improve time-in-range. CRISPR editing is being applied to engineer universal β-cell grafts (e.g. knocking out immune antigens, inserting PD-L1). Engineered gut bacteria have been shown to boost GLP-1 secretion, suggesting a new therapeutic axis. We include a comparative table of major approaches (mechanism, development stage, trials, pros/cons). Despite exciting progress, challenges remain: immune rejection, gene safety, long-term efficacy, manufacturing scale-up, cost, and ethical implications. Future research must integrate interdisciplinary advances to safely translate these biotechnologies for diverse diabetic populations.