Hossein Hakimi, Mohammad Hasan Yousefi, Zeinab Mohammadi, Sara Komeili-Movahed, Hamed Afkhami, Mohammad-Hossein Abdolmohammadi
Abstract Type 1 diabetes (T1D) is a complex autoimmune disorder that leads to the destruction of insulin-producing pancreatic beta cells. This review incorporates the established model of its pathogenesis that arises from a critical interplay between genetic susceptibility—primarily driven by HLA class II alleles—and environmental triggers, particularly enteroviral infections, through molecular mimicry. We detail the subsequent immune cascade that leads to loss of tolerance and targeted beta cell death. Building on this mechanistic foundation, this article critically assesses the evolving therapeutic landscape. This article compares transient immune-modulating strategies with transformative and potentially therapeutic approaches focused on precise genome editing (CRISPR-Cas9) and stem cell-derived beta cell replacement. We argue that the convergence of these fields engineering functional, immune-evasive beta cells and deploying them in an immune-modulated environment—is the most promising path to definitive therapy. This review concludes by outlining key drug delivery challenges, including delivery safety and functional integration, that must be addressed to turn this promise into a clinical reality for patients.