The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA.
Nanoscale. 2020 Nov 5;12(42):21583-21590. doi: 10.1039/d0nr05846g.
Nucleic acid nanostructures with different chemical compositions have shown utility in biological applications as they provide additional assembly parameters and enhanced stability. The naturally occurring 2'-5' linkage in RNA is thought to be a prebiotic analogue and has potential use in antisense therapeutics. Here, we report the first instance of DNA/RNA motifs containing 2'-5' linkages. We synthesized and incorporated RNA strands with 2'-5' linkages into different DNA motifs with varying number of branch points (a duplex, four arm junction, double crossover motif and tensegrity triangle motif). Using experimental characterization and molecular dynamics simulations, we show that hybrid DNA/RNA nanostructures can accommodate interspersed 2'-5' linkages with relatively minor effect on the formation of these structures. Further, the modified nanostructures showed improved resistance to ribonuclease cleavage, indicating their potential use in the construction of robust drug delivery vehicles with prolonged stability in physiological conditions.
具有不同化学成分的核酸纳米结构在生物应用中具有实用性，因为它们提供了额外的组装参数和增强的稳定性。人们认为 RNA 中天然存在的 2'-5' 键合是一种前生物类似物，并且在反义治疗中有潜在的用途。在这里，我们报告了含有 2'-5' 键合的 DNA/RNA 基序的第一个实例。我们合成并将具有 2'-5' 键合的 RNA 链掺入到具有不同分支点数量的不同 DNA 基序中（双链体、四臂连接点、双交叉基元和张拉整体三角形基元）。使用实验表征和分子动力学模拟，我们表明，杂交 DNA/RNA 纳米结构可以容纳交错的 2'-5' 键合，而对这些结构的形成几乎没有影响。此外，修饰的纳米结构显示出对核糖核酸酶切割的增强抗性，表明它们在构建具有生理条件下延长稳定性的稳健药物输送载体方面具有潜在用途。
