Chemical modifications of adenine base editor mRNA and guide RNA expand its application scope

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 en...

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Published inNature communications Vol. 11; no. 1; p. 1979
Main Authors Jiang, Tingting, Henderson, Jordana M., Coote, Kevin, Cheng, Yi, Valley, Hillary C., Zhang, Xiao-Ou, Wang, Qin, Rhym, Luke H., Cao, Yueying, Newby, Gregory A., Bihler, Hermann, Mense, Martin, Weng, Zhiping, Anderson, Daniel G., McCaffrey, Anton P., Liu, David R., Xue, Wen
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 24.04.2020
Nature Publishing Group
Nature Portfolio
Subjects
13/106
38/109
38/22
38/23
38/77
38/88
42/40
631/208/4041/3196
631/61/201/2110
64/60
82/80
Adenine
Adenine - chemistry
Alleles
Animal diseases
Animal models
Animals
Cell culture
Cell Line
Codon
Codon, Nonsense
CRISPR
CRISPR-Cas Systems
Cystic Fibrosis - pathology
Editors
Gene Editing
Genetic modification
Genome editing
gRNA
HEK293 Cells
Humanities and Social Sciences
Humans
Mice
mRNA
multidisciplinary
Mutation
Nucleotides
Phenotype
Plasmids
Ribonucleic acid
RNA
RNA, Guide, CRISPR-Cas Systems - chemistry
RNA, Messenger - chemistry
Science
Science (multidisciplinary)
Transfection
Uridine - analogs & derivatives
Uridine - chemistry
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Abstract 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.
AbstractList 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.
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.
Abstract 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.
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.
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.
ArticleNumber 1979
Author McCaffrey, Anton P.
Henderson, Jordana M.
Liu, David R.
Anderson, Daniel G.
Zhang, Xiao-Ou
Cao, Yueying
Weng, Zhiping
Coote, Kevin
Cheng, Yi
Xue, Wen
Jiang, Tingting
Valley, Hillary C.
Newby, Gregory A.
Rhym, Luke H.
Mense, Martin
Bihler, Hermann
Wang, Qin
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SSID ssj0000391844
Score 2.6068592
Snippet CRISPR-Cas9-associated base editing is a promising tool to correct pathogenic single nucleotide mutations in research or therapeutic settings. Efficient base...
Abstract CRISPR-Cas9-associated base editing is a promising tool to correct pathogenic single nucleotide mutations in research or therapeutic settings....
Cas9 base editors are promising tools for correcting pathogenic single nucleotide mutations. Here the authors chemically modify mRNA encoding the editor and...
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proquest
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springer
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Publisher
StartPage 1979
SubjectTerms 13/106
38/109
38/22
38/23
38/77
38/88
42/40
631/208/4041/3196
631/61/201/2110
64/60
82/80
Adenine
Adenine - chemistry
Alleles
Animal diseases
Animal models
Animals
Cell culture
Cell Line
Codon
Codon, Nonsense
CRISPR
CRISPR-Cas Systems
Cystic Fibrosis - pathology
Editors
Gene Editing
Genetic modification
Genome editing
gRNA
HEK293 Cells
Humanities and Social Sciences
Humans
Mice
mRNA
multidisciplinary
Mutation
Nucleotides
Phenotype
Plasmids
Ribonucleic acid
RNA
RNA, Guide, CRISPR-Cas Systems - chemistry
RNA, Messenger - chemistry
Science
Science (multidisciplinary)
Transfection
Uridine - analogs & derivatives
Uridine - chemistry
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Title Chemical modifications of adenine base editor mRNA and guide RNA expand its application scope
URI https://link.springer.com/article/10.1038/s41467-020-15892-8
https://www.ncbi.nlm.nih.gov/pubmed/32332735
https://www.proquest.com/docview/2394521613
https://search.proquest.com/docview/2394879472
https://pubmed.ncbi.nlm.nih.gov/PMC7181807
https://doaj.org/article/063c642bedca45fb8d0878850da6e48f
Volume 11
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