Evidence map›Paper›PMID 24056590›Full record

ArticleNature communications2013

Mutants of Cre recombinase with improved accuracy.

Nikolai Eroshenko, George M Church

Abstract read
In one paragraph

Article in Nature communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed.

  1. Article
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  7. Precise excision of HTLV-1 provirus with a designer-recombinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
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  16. Review
  17. Beyond editing to writing large genomes.Nature reviews. Genetics · 2017
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Nikolai EroshenkoHarvard School of Engineering and Applied Sciences, Cambridge, MA 02138, USA.
George M Church

Funding

Causal Transcriptional Consequences of Human Genetic VariationP50HG005550 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2010 to 2014
$19.0M
NHGRI NIH HHS P50 HG005550
6 · The paper itself

Abstract

Despite rapid advances in genome engineering technologies, inserting genes into precise locations in the human genome remains an outstanding problem. It has been suggested that site-specific recombinases can be adapted towards use as transgene delivery vectors. The specificity of recombinases can be altered either with directed evolution or via fusions to modular DNA-binding domains. Unfortunately, both wild-type and altered variants often have detectable activities at off-target sites. Here we use bacterial selections to identify mutations in the dimerization surface of Cre recombinase (R32V, R32M and 303GVSdup) that improve the accuracy of recombination. The mutants are functional in bacteria, in human cells and in vitro (except for 303GVSdup, which we did not purify), and have improved selectivity against both model off-target sites and the entire E. coli genome. We propose that destabilizing binding cooperativity may be a general strategy for improving the accuracy of dimeric DNA-binding proteins.

Indexed as

Gene Transfer TechniquesRecombination, GeneticBase SequenceCell LineDNADNA-Binding ProteinsEscherichia coliHumansIntegrasesKineticsModels, MolecularMolecular Sequence DataMutationProtein MultimerizationTransgenesViral ProteinsCre recombinaseDNADNA-Binding ProteinsIntegrasesViral Proteins

Identifiers

PMID24056590
PMCPMC3972015

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.