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 <i>In vitro</i> 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.