Genome Editing Approaches to Restore β-Cell Function in Type 1 and Type 2 Diabetes

Diabetes mellitus affects more than 500 million people worldwide, and both Type 1 (T1D) and Type 2 (T2D) forms converge on a common endpoint: the loss or dysfunction of insulin-producing pancreatic β-cells. In T1D, autoimmune destruction depletes the β-cell pool. In T2D, chronic metabolic stress drives β-cell exhaustion, dedifferentiation, and apoptosis. Current therapies, including exogenous insulin, incretin-based drugs, and islet transplantation, manage symptoms but do not restore endogenous β-cell mass or achieve durable glycemic control.Genome editing has opened a new therapeutic frontier. Tools such as CRISPR-Cas9, base editors, prime editors, and epigenome editors now make it possible to correct monogenic forms of diabetes, engineer immune-evasive β-cells, reprogram alternative cell types into insulin-secreting cells, and reverse the molecular signatures of β-cell failure. Together with advances in stem cell-derived islet differentiation, encapsulation, and in vivo delivery, these approaches are moving rapidly from proof of concept toward early clinical translation.This Research Topic brings together original research, reviews, and perspectives exploring how genome and epigenome editing can be used to preserve, regenerate, or replace functional β-cells in T1D and T2D. We aim to highlight both the mechanistic insights shaping the field and the translational challenges that remain, including delivery, safety, immunogenicity, and long-term graft function.We welcome submissions covering, but not limited to:1. CRISPR-based correction of monogenic diabetes, such as MODY, neonatal diabetes, and Wolfram syndrome2. Engineering of hypoimmunogenic β-cells to evade autoimmune and allogeneic rejection, including HLA editing, PD-L1 overexpression, and CD47 strategies3. Stem cell-derived islets, including editing of hPSCs and iPSCs to enhance differentiation, maturation, and function4. In vivo β-cell regeneration through transdifferentiation of α-cells, ductal cells, or hepatocytes5. Epigenome editing to reverse β-cell dedifferentiation and restore identity genes such as PDX1, MAFA, and NKX6.16. Base and prime editing for precise, scarless correction of diabetes-associated variants7. Delivery platforms, including AAV, lipid nanoparticles, and ex vivo editing workflows for islet cells8. Protective edits against ER stress, glucotoxicity, lipotoxicity, and inflammatory cytokines9. Safety and ethical considerations, including off-target effects, long-term genomic stability, and clinical translation10. Combination strategies integrating gene editing with encapsulation, immunomodulation, or biomaterialsA curative therapy for diabetes will likely require restoring a self-regulating, durable source of insulin. Genome editing offers the precision needed to address the genetic, immunological, and metabolic drivers of β-cell loss across both major forms of the disease. By bringing together work from stem cell biology, immunology, gene therapy, and clinical endocrinology, this Research Topic aims to map the path from molecular tools to patient-ready therapies.We invite submissions of Original Research, Reviews, Mini-Reviews, Methods, Perspectives, and Opinion articles. Topic editors: Mudhir Shekha Source: https://www.frontiersin.org/research-topics/81024/genome-editing-approaches-to-restore--cell-function-in-type-1-and-type-2-diabetes