Tetrahedral Framework Nucleic Acids Induce Immune Tolerance and Prevent the Onset of Type 1 Diabetes

A failure in immune tolerance leads to autoimmune destruction of insulin-producing β-cells, leading to type 1 diabetes (T1D). Inhibiting autoreactive T cells and inducing regulatory T cells (Tregs) to re-establish immune tolerance are promising approaches to prevent the onset of T1D. Here, we investigated the ability of tetrahedral framework nucleic acids (tFNAs) to induce immune tolerance and prevent T1D in nonobese diabetic (NOD) mice. In prediabetic NOD mice, tFNAs treatment led to maintenance of normoglycemia and reduced incidence of diabetes. Moreover, the tFNAs (250 nM) treatment preserved the mass and function of β-cells, increased the frequency of Tregs, and suppressed autoreactive T cells, leading to immune tolerance. Collectively, our results demonstrate that tFNAs treatment aids glycemic control, provides β-cell protection, and prevents the onset of T1D in NOD mice by immunomodulation. These results highlight the potential of tFNAs for the prevention of autoimmune T1D.