Fuente: WIPO "tomato" The present disclosure provides programmable base editors, and methods for their production and use. A subject programmable base editor includes (1) a CRISPR-Cas fusion protein comprising a CRISPR-Cas effector protein fused to a first member of a split-protein binding pair, where the CRISPR-Cas effector protein is a nickase (e.g., nCas9) or is catalytically inactive (e.g., dCas9, dCas12 such as dCas12a), and (2) a deaminase fusion protein comprising a deaminase protein fused to a second member of the split-protein binding pair. The CRISPR-Cas effector protein and the deaminase protein are not translationally fused to one another, but are instead post-translationally bound, e.g., in some cases covalently linked via a covalent bond (e.g., an isopeptide bond) formed between the two members of the split-protein binding pair (e.g. between a catcher protein and a partner tag protein).