Nanogenetics in diabetes: converging nanoscale platforms and gene modulation for metabolic reprogramming

Diabetes is still a global health crisis characterized by progressive dysfunction of the β-cells, insulin resistance and metabolic dysregulation. Classical pharmacotherapies have the benefit of symptomatic control without long-term metabolic reprogramming. The convergence of nanotechnology and gene modulation- here termed nanogenetics- a precise, durable way to reprogram glucose-homeostasis pathways. This critical review outlines the mechanistic foundations of nanogenetic interventions in the β-cells, hepatocytes, adipose tissue, and immune-metabolic interfaces. We offer an advanced taxonomy of nanoscale platforms (lipid, polymeric, inorganic, exosomal, and stimuli-responsive carriers) in combination with gene-editing modalities (RNA interference, CRISPR, epigenome editing, and synthetic gene circuits). The mapping of translational pipelines between In vitro organoids and humanized models to current clinical trials is done keeping in mind delivery issues, safety, manufacturing requirements and ethical aspects. Mechanistic insights are further improved with multi-omics profiling, high-end imaging, and computational digital twins. Through technological innovations and translational breakthroughs, a procession of nanogenetics-based long-term remission- and, eventually, curative interventions against diabetes is outlined.