Type 1 diabetes (T1D) is a chronic metabolic disease mediated by autoimmunity. Its pathogenesis involves complex interactions between genetic susceptibility and environmental factors. Conventional T1D risk stratification primarily relies on genetic markers, islet autoantibodies, and glycemic indicators. Although these biomarkers remain indispensable in current clinical practice, they are often insufficient when used alone to accurately identify ultra-early high-risk individuals, predict disease progression rates, or support individualized preventive strategies. Consequently, more comprehensive molecular approaches are needed to improve precision risk stratification. In recent years, the rapid development of multi-omics technologies has provided new strategies for precise risk stratification of T1D. This narrative review critically evaluates how multi-omics integration strategies can improve precision risk stratification throughout the T1D disease continuum by integrating complementary molecular information from genomics, transcriptomics, proteomics, metabolomics, epigenomics, and the microbiome. Particular emphasis is placed on stage-specific biomarker discovery, multi-omics data integration frameworks, artificial intelligence-assisted prediction models, biomarker validation, and the opportunities and challenges associated with clinical translation. Current evidence suggests that integrated multi-omics approaches have the potential to improve risk prediction accuracy, distinguish heterogeneous disease trajectories, identify individuals at imminent risk of progression, and provide biologically informed targets for precision intervention. However, important challenges remain, including data harmonization, external validation, model interpretability, cost-effectiveness, and integration into routine clinical screening programs. Future research should prioritize prospective multicenter cohorts, standardized analytical pipelines, externally validated prediction models, and clinically interpretable multi-omics frameworks to facilitate the translation of precision risk stratification into routine T1D prevention and management.
Ziyi Chen, Wen-Tao Liu, Zheng Guo et al.· Frontiers in Immunology· 0 citations
Beyond their deployment as COVID-19 vaccines, lipid nanoparticles (LNPs) have emerged as versatile vehicles for therapeutic nucleic acid delivery. However, achieving efficient and cell-targeted transfection in extrahepatic tissues, particularly pancreatic β cells, remains a major challenge. Here, we develop a dual-targeting LNP engineering strategy that integrates high-throughput compositional screening with surface conjugation of β cell-specific targeting ligands to enable selective gene delivery to pancreatic β cells. Compositional optimization identified LNP formulations that achieved over a 148-fold increase in β cell transfection efficiency in vitro and more than an 8-fold increase in pancreatic selectivity in vivo compared to the Moderna LNP formulation. Surface conjugation of the ZnT8-specific monoclonal antibody (mAb43), which recognizes the zinc transporter ZnT8 highly expressed on murine β cells, further increased pancreatic transgene expression by more than 2-fold and achieved over 70% β cell transfection in murine models. To improve translational potential, we conjugated a high-affinity camelid single-domain antibody (4hD29 nanobody) targeting dipeptidyl peptidase-6 (DPP6), a biomarker enriched on human β cells, to compositionally optimized LNPs to deliver human STAT2-siRNA. These dual-targeting LNPs reduced STAT2 expression in human β cells under IFN-α stimulation to below baseline levels observed in unstimulated controls and induced > 4-fold increase in PDL1 expression. Together, this integrated LNP design for β cell-directed gene delivery establishes a versatile platform for RNA therapeutics and gene-editing applications in a pro-inflammatory type 1 diabetes context.
Di Yu, Yining Zhu, A. Roca-Rivada et al.· ACS Nano· 0 citations
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