Chemical modifications of adenine base editor mRNA and guide RNA expand its application scope
| Autor: | Gregory A. Newby, Luke H. Rhym, Hermann Bihler, Zhiping Weng, Martin Mense, Tingting Jiang, Wen Xue, Xiao-Ou Zhang, Y. Cheng, Jordana M. Henderson, H. Valley, Yueying Cao, Anton P. McCaffrey, Daniel G. Anderson, David R. Liu, Qin Wang, Kevin Coote |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CRISPR-Cas9 genome editing Cystic Fibrosis Science General Physics and Astronomy Computational biology medicine.disease_cause Transfection General Biochemistry Genetics and Molecular Biology Article Cell Line 03 medical and health sciences Mice 0302 clinical medicine Genome editing medicine Animals Humans Nucleotide Guide RNA RNA Messenger lcsh:Science Codon Uridine Alleles chemistry.chemical_classification Gene Editing Messenger RNA Mutation Multidisciplinary Nucleotides Targeted Gene Repair Adenine HEK 293 cells RNA General Chemistry Targeted gene repair 030104 developmental biology HEK293 Cells Phenotype chemistry Codon Nonsense lcsh:Q CRISPR-Cas Systems 030217 neurology & neurosurgery Plasmids RNA Guide Kinetoplastida |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-9 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | CRISPR-Cas9-associated base editing is a promising tool to correct pathogenic single nucleotide mutations in research or therapeutic settings. Efficient base editing requires cellular exposure to levels of base editors that can be difficult to attain in hard-to-transfect cells or in vivo. Here we engineer a chemically modified mRNA-encoded adenine base editor that mediates robust editing at various cellular genomic sites together with moderately modified guide RNA, and show its therapeutic potential in correcting pathogenic single nucleotide mutations in cell and animal models of diseases. The optimized chemical modifications of adenine base editor mRNA and guide RNA expand the applicability of CRISPR-associated gene editing tools in vitro and in vivo. Cas9 base editors are promising tools for correcting pathogenic single nucleotide mutations. Here the authors chemically modify mRNA encoding the editor and the gRNA to enhance editing and broaden its application. |
| Databáze: | OpenAIRE |
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