Base editing: precision chemistry on the genome and transcriptome of living cells

RNA-guided programmable nucleases from CRISPR systems generate precise breaks in DNA or RNA at specified positions. In cells, this activity can lead to changes in DNA sequence or RNA transcript abundance. Base editing is a newer genome-editing approach that uses components from CRISPR systems togeth...

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Veröffentlicht in:Nature reviews. Genetics Jg. 19; H. 12; S. 770 - 788
Hauptverfasser: Rees, Holly A, Liu, David R
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Nature Publishing Group 01.12.2018
Schlagworte:
Animals
CRISPR
CRISPR-Cas Systems
Deoxyribonucleic acid
DNA
DNA Breaks, Double-Stranded
DNA damage
DNA glycosylase
Double-stranded RNA
Editing
Endonucleases
Gene Editing - methods
Gene expression
Genome editing
Genomes
Humans
Mutation
Nuclease
Nucleotide sequence
Ribonucleic acid
RNA
RNA editing
Therapeutic applications
Transcription
Transcriptome
ISSN:1471-0056, 1471-0064, 1471-0064
Online-Zugang:Volltext
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Zusammenfassung:RNA-guided programmable nucleases from CRISPR systems generate precise breaks in DNA or RNA at specified positions. In cells, this activity can lead to changes in DNA sequence or RNA transcript abundance. Base editing is a newer genome-editing approach that uses components from CRISPR systems together with other enzymes to directly install point mutations into cellular DNA or RNA without making double-stranded DNA breaks. DNA base editors comprise a catalytically disabled nuclease fused to a nucleobase deaminase enzyme and, in some cases, a DNA glycosylase inhibitor. RNA base editors achieve analogous changes using components that target RNA. Base editors directly convert one base or base pair into another, enabling the efficient installation of point mutations in non-dividing cells without generating excess undesired editing by-products. In this Review, we summarize base-editing strategies to generate specific and precise point mutations in genomic DNA and RNA, highlight recent developments that expand the scope, specificity, precision and in vivo delivery of base editors and discuss limitations and future directions of base editing for research and therapeutic applications.
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ISSN:1471-0056
1471-0064
1471-0064
DOI:10.1038/s41576-018-0059-1