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  Expanding the genome-targeting scope and the site selectivity of high-precision base editors

Tan, J., Zhang, F., Karcher, D., & Bock, R. (2020). Expanding the genome-targeting scope and the site selectivity of high-precision base editors. Nature Communications, 11(1): 629. doi:10.1038/s41467-020-14465-z.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-9516-A Version Permalink: http://hdl.handle.net/21.11116/0000-0006-9E07-1
Genre: Journal Article

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 Creators:
Tan, J.1, Author              
Zhang, F.1, Author              
Karcher, D.1, Author              
Bock, R.1, Author              
Affiliations:
1Organelle Biology and Biotechnology, Department Bock, Max Planck Institute of Molecular Plant Physiology, Max Planck Society, ou_1753326              

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 Abstract: Base editors (BEs) are RNA-guided CRISPR-Cas-derived genome editing tools that induce single-nucleotide changes. The limitations of current BEs lie in their low precision (especially when multiple target nucleotides of the deaminase are present within the activity window) and their restriction to targets that are in proper distance from the PAM sequence. We have recently developed high-precision cytidine BEs by engineering CDA1 truncations and nCas9 fusions that predominantly edit nucleotide C−18 relative to the PAM sequence NGG. Here, by testing fusions with Cas9 variants that recognize alternative PAMs, we provide a series of high-precision BEs that greatly expand the versatility of base editing. In addition, we obtained BEs that selectively edit C−15 or C−16. We also show that our high-precision BEs can substantially reduce off-target effect. These improved base editing tools will be widely applicable in basic research, biotechnology and gene therapy.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: URI: 10.1038/s41467-020-14465-z
Other: Tan2020
DOI: 10.1038/s41467-020-14465-z
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: 629 Volume / Issue: 11 (1) Sequence Number: 629 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723