Kweon, Jiyeon Park, Soomin Jeon, Mi Yeon Lim, Kayeong Jang, Gayoung Jang, An-Hee Lee, Minyoung Seok, Cheong Lee, Chaeyeon Park, Subin Ahn, Jiseong Jang, JiYoon Kim, Naheun Sung, Young Hoon Kim, Daesik Kim, Yongsub 2025-12-23T06:30:46Z 2025-12-23T06:30:46Z 2025-12-19 2025-11 1525-0016 https://pubs.kist.re.kr/handle/201004/153860 CRISPR-based cytosine base editors enable precise genome editing without inducing double-stranded DNA breaks yet traditionally depend on a limited selection of deaminases from the APOBEC/AID or TadA families. Here, we present SsCBE, a CRISPR-based cytosine base editor utilizing SsdAtox, a DYW-like deaminase derived from the toxin of Pseudomonas syringae. Strategic engineering of SsdAtox has led to remarkable improvements in the base editing efficiency (by up to 8.4-fold) and specificity for SsCBE, while concurrently reducing cytotoxicity. Exhibiting exceptional versatility, SsCBE was delivered and efficiently applied using diverse delivery methods, including engineered virus-like particles. Its application has enabled targeted cytosine base editing in mouse zygotes and pioneering edits in mitochondrial DNA. SsCBE expands the genome editing toolbox by introducing a distinct deaminase scaffold with broad utility for both basic research and potential therapeutic applications. English Nature Publishing Group High-efficiency base editing for nuclear and mitochondrial DNA with an optimized DYW-like deaminase Article 10.1016/j.ymthe.2025.08.007 1 Molecular Therapy, v.33, no.11, pp.5611 - 5623 Molecular Therapy 33 11 5611 5623 Y scie scopus 001616137200023 2-s2.0-105013675606 Biotechnology & Applied Microbiology Genetics & Heredity Medicine, Research & Experimental Biotechnology & Applied Microbiology Genetics & Heredity Research & Experimental Medicine Article OFF-TARGET GENOMIC DNA RNA