Nature has published online the research manuscript “Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis”.

This research paper is the product of a co-operation among Fan Guo research team of SCU West China Second University Hospital, Hui Yang research team of the Institute of Neuroscience of the Chinese Academy of Sciences ( CAS ), and Yixue Li research team of Institute for Computational Biology of CAS. Rui Yan, an undergraduate of SCU School of Life Sciences; Changyang Zhou, a doctoral student of the Institute of Neuroscience of the Chinese Academy of Sciences; Yidi Sun, a doctoral student of the Institute of Computational Biology, CAS; Yajing Liu, a doctoral student of Shanghai University of Science and Technology, and Erwei Zuo, a researcher of Shenzhen Institute of Agricultural Genome, Chinese Academy of Agricultural Sciences, are the first authors; and Professor Fan Guo, Dr. Hui Yang, Dr. Haibo Zhou, and Yi Li, a researcher of Hui Yang's research team, are the corresponding authors.

The results of full transcriptome RNA analysis at mixed cell and single cell levels showed that single base editing tools in DNA editing had significant RNA miss-target effect. It was the first time to prove that multiple single base editing tools such as BE3, BE3-hA3A and ABE7.10 all had RNA miss-target effect. ABE7.10 also caused a large number of mutations of oncogenes and anti-oncogenes, and had a strong risk of carcinogenesis. Three single-base editing tools were optimized by point mutation to eliminate RNA miss-target effect. Three single-base editing tools with higher accuracy were obtained for the first time, which laid an important foundation for single-base editing technology to enter clinical gene therapy.

The research work took half a year to go from experimental design to its completion. Key researchers had to continue working throughout the Chinese Spring Festival and finished this research in high efficiency. Although some foreign counterparts published similar research work in Nature and Science Advancesearlier, the excellent experimental design and experimental results of this work were finally published in Nature. These research findings are an important achievement accomplished through co-operation between multi-subject groups and multiple work units. The research has received support from the National Natural Science Foundation Committee and the Ministry of Science and Technology of China.