EditForce further elucidated the mechanism of RNA base editing by PPR proteins
EditForce has advanced the understanding of the base editing mechanism of PPR proteins by identifying amino acids that significantly influence the direction of RNA base editing (U-to-C and C-to-U) using our proprietary RNA editing technology “PPR Platform Technology.” This achievement is based on joint research with Kyushu University and was published in the academic journal Scientific Reports on February 21, 2025.
The single nucleotide substitution technology in RNA enables us to rewrite a specific nucleotide base on RNA, rather than the genome (DNA), to another base, and gains more and more attention as a new base editing technology following gene editing. We have been developing technology to edit cytidine to uridine (C-to-U), and uridine to cytidine (U-to-C) on RNA using PPR proteins. However, the mechanism determining the direction of base editing (U-to-C and C-to-U) was not fully understood, posing a challenge for applications in drug discovery and other fields.
In this paper, we created various mutants by changing the amino acid sequences at specific positions of the RNA editing PPR protein. Through analysis of these mutants, we discovered that changing specific amino acid sequences can control the direction of base editing toward U-to-C and C-to-U. Furthermore, we identified mutants that cause off-target editing at unexpected positions on RNA, shedding light on the precise base editing mechanism of PPR proteins.
The insights gained from this research on the role and importance of amino acids in the base editing mechanism of PPR proteins will lead us to further develop and improve the PPR Platform Technology to enhance the editing activity of target RNA bases and reduce off-target activity. We continue to promote research and development activities aimed at creating new pharmaceuticals.
Article Information
Ichinose, M. et al. Fine-tuning of the PPR protein directs the RNA editing activity toward C-to-U or U-to-C conversion. Sci Rep 15, 6288 (2025).
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