From random pools to precision tools: The expanding repertoire of synthetic nucleic acid catalysts

Synthetic nucleic acid catalysts serve as powerful tools to interrogate and manipulate biological processes with high specificity. Advances in in vitro selection, high-throughput sequencing, and computational design have yielded increasingly efficient and chemically diverse ribozymes and deoxyribozymes. Beyond applications in nucleic acid research and diagnostics, the study of nucleic acid catalysts offers fundamental insights into the origin of life and the RNA world hypothesis. This review covers both fundamental and applied perspectives and summarizes recent advancements in the field of in vitro evolution and the development of synthetic ribozymes and DNAzymes. The topics include the latest research on RNA-ligases and polymerase ribozymes as well as ribozymes and DNAzymes for targeted modification of RNA and peptides including novel catalysts for site-specific methylation, alkylation, and acylation. Finally, the versatility of RNA-cleaving DNAzymes as sensors and for the detection of RNA modifications, as well as the ability of DNAzymes to catalyze light-activating reactions are presented.