TY - JOUR T1 - Genome Editing With Targeted Deaminases JF - bioRxiv DO - 10.1101/066597 SP - 066597 AU - Luhan Yang AU - Adrian W. Briggs AU - Wei Leong Chew AU - Prashant Mali AU - Marc Guell AU - John Aach AU - Daniel Bryan Goodman AU - David Cox AU - Yinan Kan AU - Emal Lesha AU - Venkataramanan Soundararajan AU - Feng Zhang AU - George Church Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/07/28/066597.abstract N2 - Precise genetic modifications are essential for biomedical research and gene therapy. Yet, traditional homology-directed genome editing is limited by the requirements for DNA cleavage, donor DNA template and the endogenous DNA break-repair machinery. Here we present programmable cytidine deaminases that enable site-specific cytidine to thymidine (C-to-T) genomic edits without the need for DNA cleavage. Our targeted deaminases are efficient and specific in Escherichia coli, converting a genomic C-to-T with 13% efficiency and 95% accuracy. Edited cells do not harbor unintended genomic abnormalities. These novel enzymes also function in human cells, leading to a site-specific C-to-T transition in 2.5% of cells with reduced toxicity compared with zinc-finger nucleases. Targeted deaminases therefore represent a platform for safer and effective genome editing in prokaryotes and eukaryotes, especially in systems where DSBs are toxic, such as human stem cells and repetitive elements targeting. ER -