Threose nucleic acid has been considered a potential evolutionary progenitor of RNA because of its chemical simplicity, base pairing properties and capacity for higher-order functions such as folding and specific ligand binding. Here we report the in vitro selection of RNA-cleaving threose nucleic acid enzymes. One such enzyme, Tz1, catalyses a site-specific RNA-cleavage reaction with an observed pseudo first-order rate constant (k_obs) of 0.016 min⁻¹. The catalytic activity of Tz1 is maximal at 8 mM Mg²⁺ and remains relatively constant from pH 5.3 to 9.0. Tz1 preferentially cleaves a mutant epidermal growth factor receptor RNA substrate with a single point substitution, while leaving the wild-type intact. We demonstrate that Tz1 mediates selective gene silencing of the mutant epidermal growth factor receptor in eukaryotic cells. The identification of catalytic threose nucleic acids provides further experimental support for threose nucleic acid as an ancestral genetic and functional material. The demonstration of Tz1 mediating selective knockdown of intracellular RNA suggests that functional threose nucleic acids could be developed for future biomedical applications.

苏糖核酸已被认为是 RNA 的潜在进化祖细胞，因为它具有化学简单性、碱基配对特性和高级功能（如折叠和特定配体结合）的能力。在这里，我们报告了 RNA 切割苏糖核酸酶的体外选择。其中一种酶 Tz1 催化位点特异性 RNA 切割反应，观察到的伪一级速率常数 ( k _obs ) 为 0.016 分钟^-1。^{Tz1 的催化活性在 8 mM Mg 2+}时最大并且在 pH 值 5.3 到 9.0 之间保持相对恒定。Tz1 优先通过单点替换切割突变的表皮生长因子受体 RNA 底物，同时保持野生型完好无损。我们证明 Tz1 介导真核细胞中突变表皮生长因子受体的选择性基因沉默。催化苏糖核酸的鉴定为苏糖核酸作为祖先遗传和功能材料提供了进一步的实验支持。Tz1 介导细胞内 RNA 选择性敲低的证明表明，可以为未来的生物医学应用开发功能性苏糖核酸。