Utilizing AAV-mediated LEAPER 2.0 for programmable RNA editing in non-human primates and nonsense mutation correction in humanized Hurler syndrome mice.

"availability of data and materials raw data of off-target analysis are available as a bioproject with project identifier prjca019441 in the china national center for bioinformation-national genomics data center database (gsa number: cra012452) [ 43 ]. availability of data and materials raw data of off-target analysis are available as a bioproject with project identifier prjca019441"

"Declarations Ethics approval and consent to participateAll NHP studies were accredited by AAALAC International (Association for Assessment and Accreditation of Laboratory Animal Care International). The content and procedures related to animal testing are in accordance with the regulations of the Institutional Animal Care and Use Committee (IACUC) and the 8th Edition of the Institute of Laboratory Animal Resources, National Research Council, 2011. There were no alternatives to this test, and the test was not repeated. Animal numbers were designed according to the appropriate guidelines. This experiment has been approved by the Institutional IACUC of WestChina-Frontier Pharmatech Co., Ltd., approval number: IACUC-B2021025-T005-01, IACUC-B2021025-T005-02, IACUC-B2021025-T005-03, IACUC-B2021025-T005-04, IACUC-B2021025-T005-05. The mouse experiments were approved by the Peking University Laboratory Animal Center (Beijing) and undertaken in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals. Competing interestsA patent has been filed relating to the data presented. P.Y. and Y.Z. are coinventors on patent applications describing circ-arRNA targeting human IDUA W402X mutation. P.Y., Y.Z., Zexuan Yi., G.T., Yongjian Zhang, W.Z., Ying Zhao, H.X., Y.N., X.S., L.X., and L.D. are employees of EdiGene Inc. W.W. is a founder and scientific advisor for EdiGene, Inc. The other authors declare no competing interests. Competing interests A patent has been filed relating to the data presented. P.Y. and Y.Z. are coinventors on patent applications describing circ-arRNA targeting human IDUA W402X mutation. P.Y., Y.Z., Zexuan Yi., G.T., Yongjian Zhang, W.Z., Ying Zhao, H.X., Y.N., X.S., L.X., and L.D. are employees of EdiGene Inc. W.W. is a founder and scientific advisor for EdiGene, Inc. The other authors declare no competing interests."

"Funding This project was supported by funds from the National Science Foundation of China (NSFC31930016), the Beijing Advanced Innovation Center for Genomics at Peking University and the Peking-Tsinghua Center for Life Sciences (to W.W.), and the Fellowship of China Postdoctoral Science Foundation (to Z.Y.)."