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

Abstract

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.

Treatment effect of DNA framework nucleic acids on diffuse microvascular endothelial cell injury after subarachnoid hemorrhage

“… 9 Our results corroborated with the regulatory effect of tFNAs in cellular biological functions such as migration, proliferation, differentiation, and autophagy and further suggest potent biological functions with practical importance for critically injured terminally differentiated cells such as BMECs. 11 , 12 , 13 …”

“… 10 Extensive studies have revealed that tFNAs alone can regulate several cellular processes, such as migration, proliferation, differentiation, and autophagy. 11 , 12 , 13 Our previous research reported that tFNAs have beneficial effects on normal endothelial cells under physiological conditions, regulating cell viability and promoting angiogenesis. 14 Furthermore, abundant evidence has confirmed that tFNAs successfully alleviate apoptosis of various cell types by restoring normal nuclear morphology, reversing cell cycle abnormalities, and affecting apoptosis mediators.…”

Tetrahedral framework nucleic acids-based delivery of microRNA-155 inhibits choroidal neovascularization by regulating the polarization of macrophages

“…The tFNAs are a three-dimensional structure synthesized from four pieces of single strand DNA [ [23] , [24] , [25] ]. Due to the source of its components, its good biosafety and biocompatibility have been proven in previous studies [ [26] , [27] , [28] ]. In addition, accumulating evidence shows that tFNAs quickly penetrate cells and enter mammalian cells through pore-mediated endocytosis due to their special three-dimensional structure and remain intact for up to 48 h [ [29] , [30] , [31] ].…”

Application of Programmable Tetrahedral Framework Nucleic Acid-Based Nanomaterials in Neurological Disorders: Progress and Prospects

“…So, could it be the outcome of the interaction among other systems? The question listed here is from a recent data that tFNA itself had the potential ability of immunomodulatory (Gao et al, 2021). Therefore, there is a thrilling direction for us to dig in and also the next goal to achieve.…”

“…Another important question whether tFNA-based nanomaterials or their metabolites could be aggregated and exert toxicity in the brain is not clear. According to a recent study, tFNA exhibited immunomodulatory capability in decreasing the percentage of Th1 cell subgroup and inducing Treg differentiation (Gao et al, 2021). But there are still several critical issues to be studied.…”