Catalytic DNA articles from across Nature Portfolio

RNA viruses have been responsible for large-scale epidemics and pandemics throughout the last few centuries. Here, the authors show the design, synthesis and screening of artificial RNA endonuclease XNAzymes capable of cleaving genomic SARS-CoV-2 RNA and self-assembling into enzymatic nanostructures inhibiting cellular viral replication.

Engineered RNA endonuclease XNAzymes can specifically target individual disease-associated non-coding RNAs (ncRNAs) in vitro with potential as platform technology for precision detection or knockdown of individual microRNAs or longer ncRNAs.

Oligonucleotide catalysts such as ribozymes and DNAzymes can cleave RNA efficiently and specifically but are typically dependent on high concentrations of divalent cations, limiting their biological applications. A modular XNAzyme catalyst composed of 2′-deoxy-2′-fluoro-β-d-arabino nucleic acid (FANA) has now been developed that can cleave long (>5 kb), highly structured mRNAs under physiological conditions and enables allele-specific catalytic RNA knockdown inside cells.

DNAzymes are attractive catalysts for biomedical and biotechnological applications, but their catalytic mechanism remained obscure. This work investigates the detailed reaction mechanism of RNA ligation catalysed by the 9DB1 DNAzyme, revealing that it resembles those of natural protein enzymes.