This article covers the triazole-linked nucleic acids where the triazole linkage (TL) replaces the natural phosphate backbone. The replacement is done at either a few selected linkages or all the phosphate linkages. Two triazole linkages, the four-atom TL1 and the six-atom TL2, have been discussed in detail. These triazole-modified oligonucleotides have found a wide range of applications, from therapeutics to synthetic biology. For example, the triazole-linked oligonucleotides have been used in the antisense oligonucleotide (ASO), small interfering RNA (siRNA) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology as therapeutic agents. Due to the ease of the synthesis and a wide range of biocompatibility, the triazole linkage TL2 has been used to assemble a functional 300-mer DNA from alkyne- and azide-functionalized 100-mer oligonucleotides as well as an epigenetically modified variant of a 335 base-pair gene from ten short oligonucleotides. These outcomes highlight the potential of triazole-linked nucleic acids and open the doors for other TL designs and artificial backbones to fully exploit the vast potential of artificial nucleic acids in therapeutics, synthetic biology and biotechnology.

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三唑连接的核酸：合成、治疗和合成生物学应用

本文介绍了三唑连接的核酸，其中三唑键 (TL) 取代了天然磷酸酯主链。替换是在几个选定的键或所有磷酸键上完成的。已经详细讨论了两个三唑键，即四原子 TL1 和六原子 TL2。这些三唑修饰的寡核苷酸具有广泛的应用，从治疗到合成生物学。例如，三唑连接的寡核苷酸已被用于反义寡核苷酸（ASO）、小干扰RNA（siRNA）和成簇规则间隔短回文重复（CRISPR）-Cas9技术作为治疗剂。由于易于合成和广泛的生物相容性，三唑键 TL2 已被用于从炔烃和叠氮化物功能化的 100 聚体寡核苷酸组装功能性 300 聚体 DNA 以及 335 的表观遗传修饰变体。来自十个短寡核苷酸的碱基对基因。这些结果凸显了三唑连接核酸的潜力，并为其他 TL 设计和人工主链打开了大门，以充分利用人工核酸在治疗、合成生物学和生物技术方面的巨大潜力。