Newly Discovered Deaminase Protein Clusters Enable Better DNA Editing

Using artificial intelligence-based methods, researchers from the Chinese Academy of Sciences have discovered novel deaminase proteins with unique functions. "This approach could open up a range of applications for the discovery and creation of desired plant genetic traits. In their paper, which is published in the journal Cell, the researchers use AlphaFold2 to predict the structures of proteins within the deaminase protein family based on structural similarities. This approach led to the identification of five new deaminase clusters with cytidine deamination activity in the context of DNA base editors. They also reclassified a group of cytidine deaminases called SCP1.201 that perform deamination primarily on single-stranded DNA and developed a suite of new DNA base editors. "These deaminases exhibit properties such as higher efficiency, lower generation of off-target editing events, editing at different preferred sequence motifs, and much smaller size," the authors write. Meanwhile, they also developed the smallest single-strand specific cytidine deaminase, which allows an efficient cytosine base editor to be packaged in a single adeno-associated virus. These deaminases greatly expand the utility of base editors for therapeutic and agricultural applications, the authors say.