For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
11
views
12
references
 Top references
cited by
326
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      217
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Base editors enable targeted single-nucleotide conversion in genomic DNA. Here we show that expression levels are a bottleneck in base editing efficiency. We optimize cytidine (BE4) and adenine (ABE7.10) base editors by modification of nuclear localization signals and codon usage, and ancestral reconstruction of the deaminase component. The resulting BE4max, AncBE4max, and ABEmax editors correct pathogenic SNPs with substantially increased efficiency in a variety of mammalian cell types.

          Related collections

          Most cited references12

          • Record: found
          • Abstract: not found
          • Article: not found

          Basic Local Alignment Search Tool

          S Altschul (1990)
          Article 0 comments Cited 1462 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Increasing the genome-targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions

            Y Bill Kim, Alexis Komor, Jonathan Levy … (2017)
            Base editing is a recently developed approach to genome editing that uses a fusion protein containing a catalytically defective Streptococcus pyogenes Cas9, a cytidine deaminase, and an inhibitor of base excision repair to induce programmable, single-nucleotide changes in the DNA of living cells without generating double-strand DNA breaks, without requiring a donor DNA template, and without inducing an excess of stochastic insertions and deletions 1 . Here we report the development of five new C→T (or G→A) base editors that use natural and engineered Cas9 variants with different protospacer-adjacent motif (PAM) specificities to expand the number of sites that can be targeted by base editing by 2.5-fold. Additionally, we engineered new base editors containing mutated cytidine deaminase domains that narrow the width of the apparent editing window from approximately 5 nucleotides to as little as 1 to 2 nucleotides, enabling the discrimination of neighboring C nucleotides that would previously be edited with comparable efficiency, thereby doubling the number of disease-associated target Cs that can be corrected preferentially over nearby non-target Cs. Collectively, these developments substantially increase the targeting scope of base editing and establish the modular nature of base editors.
            Article 0 comments Cited 372 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Codon optimality, bias and usage in translation and mRNA decay

              Gavin Hanson, Jeff Coller (2017)
              The advent of ribosome profiling and other tools to probe mRNA translation has revealed that codon bias - the uneven use of synonymous codons in the transcriptome - serves as a secondary genetic code: a code that guides the efficiency of protein production, the fidelity of translation and the metabolism of mRNAs. Recent advancements in our understanding of mRNA decay have revealed a tight coupling between ribosome dynamics and the stability of mRNA transcripts; this coupling integrates codon bias into the concept of codon optimality, or the effects that specific codons and tRNA concentrations have on the efficiency and fidelity of the translation machinery. In this Review, we first discuss the evidence for codon-dependent effects on translation, beginning with the basic mechanisms through which translation perturbation can affect translation efficiency, protein folding and transcript stability. We then discuss how codon effects are leveraged by the cell to tailor the proteome to maintain homeostasis, execute specific gene expression programmes of growth or differentiation and optimize the efficiency of protein production.
              Article 0 comments Cited 262 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-journal-id): 9604648
                Journal ID (pubmed-jr-id): 20305
                Journal ID (nlm-ta): Nat Biotechnol
                Journal ID (iso-abbrev): Nat. Biotechnol.
                Title: Nature biotechnology
                ISSN (Print): 1087-0156
                ISSN (Electronic): 1546-1696
                Publication date Nihms-submitted: 22 May 2018
                Publication date (Electronic): 29 May 2018
                Publication date (Print): October 2018
                Publication date PMC-release: 29 November 2018
                Volume: 36
                Issue: 9
                Pages: 843-846
                Affiliations
                [1 ]Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
                [2 ]Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA
                [3 ]Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA
                Author notes
                [* ]Correspondence should be addressed to David R. Liu: drliu@ 123456fas.harvard.edu
                Article
                Manuscript ID: NIHMS969743
                DOI: 10.1038/nbt.4172
                PMC ID: 6126947
                PubMed ID: 29813047
                SO-VID: 818c40d7-c240-45a3-92bf-56859b87c348
                License:

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Categories
                Subject: Article

                ScienceOpen disciplines: Biotechnology
                Data availability:
                ScienceOpen disciplines: Biotechnology

                Comments

                Comment on this article

                scite_

                Similar content217

                See all similar

                Cited by407

                See all cited by