Single-base editors,including cytosine base editors(CBEs)and adenine base editors(ABEs),facilitate accurate C·G to T·A and A·T to G·C,respectively,holding promise for the precise modeling and treat...Single-base editors,including cytosine base editors(CBEs)and adenine base editors(ABEs),facilitate accurate C·G to T·A and A·T to G·C,respectively,holding promise for the precise modeling and treatment of human hereditary disorders.Efficient base editing and expanded base conversion range have been achieved in human cells through base editors fusing with Rad51 DNA binding domain(Rad51DBD),such as hyA3A-BE4max.Here,we show that hyA3A-BE4max catalyzes C-to-T substitution in the zebrafish genome and extends editing positions(C_(12)-C_(16))proximal to the protospacer adjacent motif.We develop a codon-optimized counterpart zhyA3A-CBE5,which exhibits substantially high C-to-T conversion with 1.59-to 3.50-fold improvement compared with the original hyA3A-BE4max.With these tools,disease-relevant hereditary mutations can be more efficaciously generated in zebrafish.We introduce human genetic mutation rpl11^(Q42*)and abcc6a^(R1463C) by zhyA3A-CBE5 in zebrafish,mirroring Diamond-Blackfan anemia and Pseudoxanthoma Elasticum,respectively.Our study expands the base editing platform targeting the zebrafish genomic landscape and the application of single-base editors for disease modeling and gene function study.展开更多
为了提高介质阻挡放电(d ielectric barrier d ischarge,DBD)等离子体的处理效率,研究了内外介质组成分别为:(1)石英+石英;(2)陶瓷+石英;(3)陶瓷+陶瓷这3种情况下苯的降解情况。试验结果表明,在处理低浓度含苯废气时,陶瓷+陶瓷效果最好...为了提高介质阻挡放电(d ielectric barrier d ischarge,DBD)等离子体的处理效率,研究了内外介质组成分别为:(1)石英+石英;(2)陶瓷+石英;(3)陶瓷+陶瓷这3种情况下苯的降解情况。试验结果表明,在处理低浓度含苯废气时,陶瓷+陶瓷效果最好;陶瓷(内管)+石英(外管)在处理高浓度含苯废气时显示出优势。通过对气相产物和固相结焦产物的分析验证了DBD能有效降解苯,降解产物不会带来新的污染。进一步分析了实验条件和介质材料的变化对DBD降解苯的影响机理。展开更多
基金supported by grants from Ministry of Science and Technology of the People's Republic of China(2018YFA0801004 and 2018YFA0800103)the National Natural Science Foundation of China(NSFC31530044,NSFC31970780,NSFC82202056).
文摘Single-base editors,including cytosine base editors(CBEs)and adenine base editors(ABEs),facilitate accurate C·G to T·A and A·T to G·C,respectively,holding promise for the precise modeling and treatment of human hereditary disorders.Efficient base editing and expanded base conversion range have been achieved in human cells through base editors fusing with Rad51 DNA binding domain(Rad51DBD),such as hyA3A-BE4max.Here,we show that hyA3A-BE4max catalyzes C-to-T substitution in the zebrafish genome and extends editing positions(C_(12)-C_(16))proximal to the protospacer adjacent motif.We develop a codon-optimized counterpart zhyA3A-CBE5,which exhibits substantially high C-to-T conversion with 1.59-to 3.50-fold improvement compared with the original hyA3A-BE4max.With these tools,disease-relevant hereditary mutations can be more efficaciously generated in zebrafish.We introduce human genetic mutation rpl11^(Q42*)and abcc6a^(R1463C) by zhyA3A-CBE5 in zebrafish,mirroring Diamond-Blackfan anemia and Pseudoxanthoma Elasticum,respectively.Our study expands the base editing platform targeting the zebrafish genomic landscape and the application of single-base editors for disease modeling and gene function study.
文摘为了提高介质阻挡放电(d ielectric barrier d ischarge,DBD)等离子体的处理效率,研究了内外介质组成分别为:(1)石英+石英;(2)陶瓷+石英;(3)陶瓷+陶瓷这3种情况下苯的降解情况。试验结果表明,在处理低浓度含苯废气时,陶瓷+陶瓷效果最好;陶瓷(内管)+石英(外管)在处理高浓度含苯废气时显示出优势。通过对气相产物和固相结焦产物的分析验证了DBD能有效降解苯,降解产物不会带来新的污染。进一步分析了实验条件和介质材料的变化对DBD降解苯的影响机理。
