Engineered TnpB genome editors for plants and human cells identified by ribonucleoprotein mutational scanning

TnpB is a diverse family of RNA-guided endonucleases associated with prokaryotic transposons. Because of their small size and putative evolutionary relationship to CRISPR-Cas12, TnpB enzymes hold great potential for genome editing. However, most TnpBs lack robust gene-editing activity. Here, we mapped comprehensive sequence-function landscapes of a TnpB ribonucleoprotein using deep mutational scanning and we discovered activating mutations in both the RNA and the protein. Leveraging the protein'