File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Parallel engineering and activity profiling of a base editor system

TitleParallel engineering and activity profiling of a base editor system
Authors
Keywordsbase editing
combinatorial assembly
CombiSEAL
CRISPR
deaminase
editing outcome
genome editing
guide RNA scaffold
high-throughput screening
precise genome editor
Issue Date9-May-2023
PublisherElsevier
Citation
Cell Systems, 2023, v. 14, n. 5, p. 392-403 How to Cite?
Abstract

Selecting the most suitable existing base editors and engineering new variants for installing specific base conversions with maximal efficiency and minimal undesired edits are pivotal for precise genome editing applications. Here, we present a platform for creating and analyzing a library of engineered base editor variants to enable head-to-head evaluation of their editing performance at scale. Our comprehensive comparison provides quantitative measures on each variant’s editing efficiency, purity, motif preference, and bias in generating single and multiple base conversions, while uncovering undesired higher indel generation rate and noncanonical base conversion for some of the existing base editors. In addition to engineering the base editor protein, we further applied this platform to investigate a hitherto underexplored engineering route and created guide RNA scaffold variants that augment the editor’s base-editing activity. With the unknown performance and compatibility of the growing number of engineered parts including deaminase, CRISPR-Cas enzyme, and guide RNA scaffold variants for assembling the expanding collection of base editor systems, our platform addresses the unmet need for an unbiased, scalable method to benchmark their editing outcomes and accelerate the engineering of next-generation precise genome editors.


Persistent Identifierhttp://hdl.handle.net/10722/329188
ISSN
2023 Impact Factor: 9.0
2023 SCImago Journal Rankings: 4.872
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFong, JHC-
dc.contributor.authorChu, HY-
dc.contributor.authorZhou, P-
dc.contributor.authorWong, SLA-
dc.date.accessioned2023-08-05T07:55:57Z-
dc.date.available2023-08-05T07:55:57Z-
dc.date.issued2023-05-09-
dc.identifier.citationCell Systems, 2023, v. 14, n. 5, p. 392-403-
dc.identifier.issn2405-4712-
dc.identifier.urihttp://hdl.handle.net/10722/329188-
dc.description.abstract<p>Selecting the most suitable existing base editors and engineering new variants for installing specific base conversions with maximal efficiency and minimal undesired edits are pivotal for precise genome editing applications. Here, we present a platform for creating and analyzing a library of engineered base editor variants to enable head-to-head evaluation of their editing performance at scale. Our comprehensive comparison provides quantitative measures on each variant’s editing efficiency, purity, motif preference, and bias in generating single and multiple base conversions, while uncovering undesired higher indel generation rate and noncanonical base conversion for some of the existing base editors. In addition to engineering the base editor protein, we further applied this platform to investigate a hitherto underexplored engineering route and created guide RNA scaffold variants that augment the editor’s base-editing activity. With the unknown performance and compatibility of the growing number of engineered parts including deaminase, CRISPR-Cas enzyme, and guide RNA scaffold variants for assembling the expanding collection of base editor systems, our platform addresses the unmet need for an unbiased, scalable method to benchmark their editing outcomes and accelerate the engineering of next-generation precise genome editors.</p>-
dc.languageeng-
dc.publisherElsevier-
dc.relation.ispartofCell Systems-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectbase editing-
dc.subjectcombinatorial assembly-
dc.subjectCombiSEAL-
dc.subjectCRISPR-
dc.subjectdeaminase-
dc.subjectediting outcome-
dc.subjectgenome editing-
dc.subjectguide RNA scaffold-
dc.subjecthigh-throughput screening-
dc.subjectprecise genome editor-
dc.titleParallel engineering and activity profiling of a base editor system-
dc.typeArticle-
dc.identifier.doi10.1016/j.cels.2023.03.007-
dc.identifier.scopuseid_2-s2.0-85158817286-
dc.identifier.volume14-
dc.identifier.issue5-
dc.identifier.spage392-
dc.identifier.epage403-
dc.identifier.eissn2405-4712-
dc.identifier.isiWOS:001054382400001-
dc.identifier.issnl2405-4712-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats