Evidence map›Paper›PMID 24270794›Full record

ArticleNucleic acids research2014

Reprogramming homing endonuclease specificity through computational design and directed evolution.

Summer B Thyme, Sandrine J S Boissel, S Arshiya Quadri, Tony Nolan, Dean A Baker, Rachel U Park, Lara Kusak, Justin Ashworth, David Baker

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
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

19 citing papers in PubMed, 40 citations in OpenAlex.

  1. Deletions of DNA in cancer and their possible uses for therapy.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Cleave and Rescue, a novel selfish genetic element and general strategy for gene drive.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  9. Article
  10. Review
  11. Applications of Alternative Nucleases in the Age of CRISPR/Cas9.International journal of molecular sciences · 2017
    Review
  12. Article
  13. Article
  14. Salient Features of Endonuclease Platforms for Therapeutic Genome Editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Review
  15. Article
  16. Structure-based modeling of protein: DNA specificity.Briefings in functional genomics · 2015
    Review
  17. Article
  18. Review
  19. Review
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

9 authors at 1 institution in 1 country.

Summer B ThymeDepartment of Biochemistry, University of Washington, UW Box 357350, 1705 NE Pacific St., Seattle, WA 98195, USA, Graduate Program in Biomolecular Structure and Design, University of Washington, UW Box 357350, 1705 NE Pacific St., Seattle, WA 98195, USA, Graduate Program in Molecular and Cellular Biology, University of Washington, UW Box 357275, 1959 NE Pacific St., Seattle, WA 98195, USA, Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, Imperial College Road, London SW7 2AZ, UK, Department of Genetics, University of Cambridge, Downing Street, Cambridge CB1 3QA, UK, Institute for Systems Biology, 401 Terry Avenue N, Seattle, WA 98109, USA and Howard Hughes Medical Institute, University of Washington, UW Box 357350, 1705 NE Pacific St., Seattle, WA 98195, USA.
Sandrine J S Boissel
S Arshiya Quadri
Tony Nolan
Dean A Baker
Rachel U Park
Lara Kusak
Justin Ashworth
David Baker
University of Washington · US

Funding

Directed Protein Evolution for Design of LAGLIDADGs with Novel Recognition SpeciRL1CA133832 · NCI · SEATTLE CHILDREN'S HOSPITAL · PI SCHARENBERG, ANDREW M. · 2007 to 2011
$2.2M
Computational Design of an LAGLIDADGs with Novel Recognition Specificities (CompoRL1GM084433 · NIGMS · UNIVERSITY OF WASHINGTON · PI BAKER, DAVID · 2007 to 2011
$1.9M
Howard Hughes Medical InstituteNCI NIH HHS RL1CA133832NIGMS NIH HHS GM084433
6 · The paper itself

Abstract

Homing endonucleases (HEs) can be used to induce targeted genome modification to reduce the fitness of pathogen vectors such as the malaria-transmitting Anopheles gambiae and to correct deleterious mutations in genetic diseases. We describe the creation of an extensive set of HE variants with novel DNA cleavage specificities using an integrated experimental and computational approach. Using computational modeling and an improved selection strategy, which optimizes specificity in addition to activity, we engineered an endonuclease to cleave in a gene associated with Anopheles sterility and another to cleave near a mutation that causes pyruvate kinase deficiency. In the course of this work we observed unanticipated context-dependence between bases which will need to be mechanistically understood for reprogramming of specificity to succeed more generally.

Indexed as

AnimalsAnophelesBacteriaComputational BiologyDirected Molecular EvolutionDNA CleavageEndodeoxyribonucleasesGenes, InsectModels, MolecularProtein EngineeringSubstrate SpecificityEndodeoxyribonucleases

Identifiers

PMID24270794
PMCPMC3936771
OpenAlexW2133854433

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.