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Enzymatic Synthesis of TNA Protects DNA Nanostructures
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DOI：10.1002/anie.202317334.png)
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Abstract
En 中文
Xeno-nucleic acids (XNAs) are synthetic genetic polymers with improved biological stabilities and offer powerful molecular tools such as aptamers and catalysts. However, XNA application has been hindered by a very limited repertoire of tool enzymes, particularly those that enable de novo XNA synthesis. Here we report that terminal deoxynucleotide transferase (TdT) catalyzes untemplated threose nucleic acid (TNA) synthesis at the 3' terminus of DNA oligonucleotide, resulting in DNA-TNA chimera resistant to exonuclease digestion. Moreover, TdT-catalyzed TNA extension supports one-pot batch preparation of biostable chimeric oligonucleotides, which can be used directly as staple strands during self-assembly of DNA origami nanostructures (DONs). Such TNA-protected DONs show enhanced biological stability in the presence of exonuclease I, DNase I and fetal bovine serum. This work not only expands the available enzyme toolbox for XNA synthesis and manipulation, but also provides a promising approach to fabricate DONs with improved stability under the physiological condition. Terminal deoxynucleotidyl transferase (TdT) accepts threose nucleic acid (TNA) nucleotide substrates, and catalyzes de novo synthesis of TNA on the 3' ends of DNA oligonucleotides. The TNA extension protects DNAs from nuclease digestion, and the DNA-TNA chimeras are used directly as staple strands in the self-assembly of DNA origami nanostructures (DONs). The TNA-shielded DONs are more biologically stable under the physiological environment.+ image
Keywords:
DNA nanotechnology
threose nucleic acid
DNA chemical modification
nuclease resistance
terminal deoxynucleotide transferase
Journal
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