RNA base editing is a promising tool in precise molecular therapy. Currently, there are two widely used RNA base editors, REPAIRand RESCUE. REPAIR only facilitates A-to-I conversions, while RESCUE performs both A-to-I...RNA base editing is a promising tool in precise molecular therapy. Currently, there are two widely used RNA base editors, REPAIRand RESCUE. REPAIR only facilitates A-to-I conversions, while RESCUE performs both A-to-I and C-to-U conversions. Thus, RESCUEcan generate twice the number of mutations compared to REPAIR. However, transcription-wide impact due to RESCUE-induced offtarget single-nucleotide variants (SNVs) is not fully appreciated. Therefore, to determine the off-target effects of RESCUE-mediatedediting, we employed transcription-wide sequencing on cells edited by RESCUE. The SNVs showed different off-target effects onmRNA, circRNA, lncRNA, and miRNA expression patterns and their interacting networks. Our results illustrate the transcriptionwide impact of RESCUE-induced off-target SNVs and highlight the need for careful characterization of the off-target impact by thisediting platform.展开更多
基金supported by grants from the Ministry of Agriculture of China(2016ZX08009003-006 and 2011ZX08006-001)the National Key Laboratory Open Fund Project(2020SKLAB6-24)+1 种基金the ZJU-Hangzhou Global Scientific and Technological Innovation Center,Zhejiang University(02020200-K02013008)the National Natural Science Foundation of China(32071347).
文摘RNA base editing is a promising tool in precise molecular therapy. Currently, there are two widely used RNA base editors, REPAIRand RESCUE. REPAIR only facilitates A-to-I conversions, while RESCUE performs both A-to-I and C-to-U conversions. Thus, RESCUEcan generate twice the number of mutations compared to REPAIR. However, transcription-wide impact due to RESCUE-induced offtarget single-nucleotide variants (SNVs) is not fully appreciated. Therefore, to determine the off-target effects of RESCUE-mediatedediting, we employed transcription-wide sequencing on cells edited by RESCUE. The SNVs showed different off-target effects onmRNA, circRNA, lncRNA, and miRNA expression patterns and their interacting networks. Our results illustrate the transcriptionwide impact of RESCUE-induced off-target SNVs and highlight the need for careful characterization of the off-target impact by thisediting platform.
