Evidence map›Paper›PMID 28180900›Full record

ArticleProtein engineering, design & selection : PEDS2017

Engineering potent long-acting variants of the Wnt inhibitor DKK2.

Richelle Sopko, Joshua W Mugford, Andreas Lehmann, Renée I Shapiro, Mia Rushe, Abhishek Kulkarni, Joseph Worrall, Joseph Amatucci, Dingyi Wen, Nels E Pederson and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Protein engineering, design & selection : PEDS, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.1field-weighted citation impact, top 51% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. 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

13 authors at 1 institution in 1 country.

Richelle SopkoDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Joshua W MugfordDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Andreas LehmannDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Renée I ShapiroDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Mia RusheDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Abhishek KulkarniDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Joseph WorrallDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Joseph AmatucciDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Dingyi WenDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Nels E PedersonDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Brenda K MinesingerDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Joseph W ArndtDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Blake PepinskyDepartment of Cell and Protein Sciences, Biogen, Cambridge, MA 02142, USA.
Biogen (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Wnt signaling pathways are required for a wide variety of biological processes ranging from embryonic development to tissue repair and regeneration. Dickkopf-2 (DKK2) is classically defined as a canonical Wnt inhibitor, though it may play a role in activating non-canonical Wnt pathways in the context of endothelial network formation after acute injury. Here we report the discovery of a fusion partner for a DKK2 polypeptide that significantly improves the expression, biochemical properties and pharmacokinetics (PK) of the DKK2 polypeptide. Specifically, human serum albumin (HSA) was identified as a highly effective fusion partner. Substitution of selected amino acid residues in DKK2 designed to decrease heparan sulfate binding by HSA-DKK2 variants, further improved the PK properties of the molecule in rodents. The HSA-DKK2 variants were monomeric, as thermally stable as wild type, and active as measured by their ability to bind to and prevent phosphorylation of the Wnt coreceptor LRP6. Our engineering efforts resulted in potent long-lived variants of the canonical Wnt inhibitor DKK2, applicable for Wnt pathway manipulation either by systematic delivery or focused administration at sites of tissue injury.

Indexed as

Intercellular Signaling Peptides and ProteinsProtein EngineeringRecombinant Fusion ProteinsSerum AlbuminAnimalsHumansLow Density Lipoprotein Receptor-Related Protein-6MiceWnt ProteinsWnt Signaling PathwayDkk2 protein, mouseIntercellular Signaling Peptides and ProteinsLow Density Lipoprotein Receptor-Related Protein-6Lrp6 protein, mouseRecombinant Fusion ProteinsSerum AlbuminWnt ProteinsDickkopf-2heparan sulfatehuman serum albumintissue injuryWnt signaling

Identifiers

PMID28180900
PMCPMC5425732
OpenAlexW2587486970

What OpenQuestion holds

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LicenceCC BY-NC
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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.