Core Viewpoint - The article discusses advancements in base editing technology, specifically focusing on the development of high-precision cytosine base editors (CBE) to enhance the accuracy of genetic modifications, which is crucial for clinical applications [3][7]. Group 1: Base Editing Technology - Base editors are created by fusing cytosine deaminase or adenine deaminase with a CRISPR protein that has lost nuclease activity, allowing for specific base conversions in the genome [2]. - Current base editors modify all cytosines or adenines within the editing window, which limits their precision [3]. Group 2: Research Development - A research team from the University of Chicago published a study in Nature Biotechnology, focusing on evolving nucleic-acid-recognition hotspots in deaminase to develop high-precision CBEs [3][6]. - The study involved the directed evolution of the tRNA-specific adenine deaminase (TadA) from E. coli to address the issue of non-specific editing in existing base editors [4][5]. Group 3: Results and Applications - The research team developed 16 variants of TadA that cover all possible -1 and +1 contexts for target cytosine editing, providing customizable deaminases for base editing [5]. - These variants were applied to correct disease-related T:A to C:G conversions with an accuracy improvement of 81.5% compared to traditional base editors [6]. - The study also simulated two cancer-driving mutations, KRAS G12D and TP53 R248Q, demonstrating the practical applications of the developed high-precision CBEs [6].