Evidence map›Paper›PMID 21784983›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

Tapping natural reservoirs of homing endonucleases for targeted gene modification.

Ryo Takeuchi, Abigail R Lambert, Amanda Nga-Sze Mak, Kyle Jacoby, Russell J Dickson, Gregory B Gloor, Andrew M Scharenberg, David R Edgell, Barry L Stoddard

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

56 citing papers in PubMed, 99 citations in OpenAlex.

  1. Article
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  6. ACS synthetic biology · 2023
    Article
  7. Review
  8. The mitogenomes ofFrontiers in microbiology · 2023
    Article
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  10. Review
  11. The Mitogenomes ofFrontiers in microbiology · 2021
    Article
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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 3 institutions in 2 countries.

Ryo TakeuchiDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North A3-025, Seattle, WA 98109, USA.
Abigail R Lambert
Amanda Nga-Sze Mak
Kyle Jacoby
Russell J Dickson
Gregory B Gloor
Andrew M Scharenberg
David R Edgell
Barry L Stoddard
Fred Hutch Cancer Center · USWestern University · CAUniversity of Washington · US

Funding

Structure, function &engineering of nuclease catalystsR01GM049857 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STODDARD, BARRY L. · 1994 to 2014
$4.2M
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
Structural and Biophysical Characterization of Engineered Homing Endonucleases (CRL1CA133833 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STODDARD, BARRY L. · 2007 to 2011
$2.1M
CIHR MOP 977800NCI NIH HHS RL1 CA133832NCI NIH HHS RL1 CA133833NIGMS NIH HHS R01 GM049857NIGMS NIH HHS R01 GM49857
6 · The paper itself

Abstract

Homing endonucleases mobilize their own genes by generating double-strand breaks at individual target sites within potential host DNA. Because of their high specificity, these proteins are used for "genome editing" in higher eukaryotes. However, alteration of homing endonuclease specificity is quite challenging. Here we describe the identification and phylogenetic analysis of over 200 naturally occurring LAGLIDADG homing endonucleases (LHEs). Biochemical and structural characterization of endonucleases from one clade within the phylogenetic tree demonstrates strong conservation of protein structure contrasted against highly diverged DNA target sites and indicates that a significant fraction of these proteins are sufficiently stable and active to serve as engineering scaffolds. This information was exploited to create a targeting enzyme to disrupt the endogenous monoamine oxidase B gene in human cells. The ubiquitous presence and diversity of LHEs described in this study may facilitate the creation of many tailored nucleases for genome editing.

Indexed as

Gene TargetingAmino Acid SequenceBase SequenceEndonucleasesHumansModels, MolecularMolecular Sequence DataMonoamine OxidaseMutagenesisProtein BindingProtein EngineeringSubstrate SpecificityEndonucleasesMonoamine Oxidase

Identifiers

PMID21784983
PMCPMC3156218
OpenAlexW2038886726

What OpenQuestion holds

Textmetadata
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.