FANAZymes: A new class of nucleic acid enzymes

In recent years, there has been diminished interest in nucleic acid enzymes. However, Taylor and colleagues’ new study on 2′-deoxy-2′-fluoro-β-d-arabino nucleic acids (FANAs) in Nature Chemistry may thrust these enzymes back into the spotlight. 1 Taylor A.I. Wan C.J.K. Donde M.J. Peak-Chew S.Y. Holliger P. A modular XNAzyme cleaves long, structured RNAs under physiological conditions and enables allele-specific gene silencing. Nat. Chem. 2022; 14: 1295-1305https://doi.org/10.1038/s41557-022-01021-z Crossref PubMed Scopus (9) Google Scholar Indeed, the Nobel prize-winning discovery that RNA can function as a site-specific RNA-cleaving enzyme by Cech, Altman, and colleagues (reviewed in Rossi 2 Rossi J.J. Ribozymes, genomics and therapeutics. Chem. Biol. 1999; 6: R33-R37https://doi.org/10.1016/S1074-5521(99)80001-5 Abstract Full Text PDF PubMed Scopus (63) Google Scholar ) prompted a flurry of investigations into ribozymes and their function. One critical advancement in this field was the discovery of the hammerhead ribozyme, a plant viroid RNA self-cleaving motif that functions by Watson-Crick base pairing flanking the GUC cleavage site. 2 Rossi J.J. Ribozymes, genomics and therapeutics. Chem. Biol. 1999; 6: R33-R37https://doi.org/10.1016/S1074-5521(99)80001-5 Abstract Full Text PDF PubMed Scopus (63) Google Scholar ,3 Forster A.C. Symons R.H. Self-cleavage of plus and minus RNAs of a virusoid and a structural model for the active sites. Cell. 1987; 49: 211-220https://doi.org/10.1016/0092-8674(87)90562-9 Abstract Full Text PDF PubMed Scopus (569) Google Scholar ,4 Haseloff J. Gerlach W.L. Simple RNA enzymes with new and highly specific endoribonuclease activities. Nature. 1988; 334: 585-591https://doi.org/10.1038/334585a0 Crossref PubMed Scopus (968) Google Scholar The therapeutic application of hammerhead ribozyme was quickly realized because it can function in trans to cleave any complementary target transcript, thereby destroying the transcript function. 4 Haseloff J. Gerlach W.L. Simple RNA enzymes with new and highly specific endoribonuclease activities. Nature. 1988; 334: 585-591https://doi.org/10.1038/334585a0 Crossref PubMed Scopus (968) Google Scholar