Researchers at the University of Florida reported a DNA-guided CRISPR–Cas12 system (ΨDNA) that directs Cas12 nucleases to RNA targets using DNA guide scaffolds rather than RNA guides. The approach, described in Nature Biotechnology, aims to expand CRISPR’s control beyond genome editing to programmable control of transcriptomes. The work builds on Cas12’s ability to act when bound to its RNA substrate, with the DNA guide designed to mimic the crRNA scaffold orientation. The platform was reported to enable RNA detection and knockdown of endogenous transcripts in human cell lines, with authors highlighting reduced instability versus RNA-guided designs. Separate reports on Nature Biotechnology publications in the same area emphasize broader technical implications, including how guide format impacts targeting and performance in RNA studies. If validated further, DNA-guided guidance could become a new modular approach for RNA therapeutics and diagnostics.