2025-12-11 九州大学
<関連情報>
- https://www.kyushu-u.ac.jp/ja/researches/view/1365
- https://www.kyushu-u.ac.jp/f/64174/25_1211_01.pdf
- https://academic.oup.com/nar/article/53/22/gkaf1309/8373960
RECODE: プログラム可能なガイドフリーのC-to-U RNA編集ツール RECODE: a programmable guide-free C-to-U RNA editing tool
Mizuho Ichinose,Masaru Ohta,Yasuka Shimajiri,Yumi Akaiwa,Izumi Nakamura,Miki Shimamoto,Riyo Makinoda,Soichi Ozaki,Takayuki Tamai,Nana Maekawa…
Nucleic Acids Research Published:08 December 2025
DOI:https://doi.org/10.1093/nar/gkaf1309
Abstract
Programmable RNA cytidine deaminase tools have been developed to convert cytidine-to-uridine (C-to-U) using CRISPR systems with guide RNAs. These tools, however, have limitations such as low editing efficiency, limited targetable sequence flexibility, and off-target RNA editing. Here, we present a novel guide-free C-to-U editing tool, named RECODE (RNA Editor for C-to-U with an Optimized DYW Enzyme), based on the RNA-binding pentatricopeptide repeat proteins, naturally fused to a C-terminal DYW cytidine deaminase domain. The RECODE specificity domain was engineered to enable retargeting, while its length and sequence were optimized to reduce off-target effects. Further optimization of the C-terminal catalytic region increased both the editing activity and the translation of the edited RNA. We showed that RECODE efficiently edits a wide range of targets in human cells, without affecting adjacent cytidines. It achieved over 50% editing efficiency for most sites, except those with an upstream guanine. Furthermore, we showed that RECODE is functional in mice, with high editing efficiency observed in specific tissues such as skeletal muscles using an AAV delivery system, suggesting its therapeutic potential for various diseases.
