Evidence map›Paper›PMID 24949974›Full record

ArticleCell2014

A computationally designed inhibitor of an Epstein-Barr viral Bcl-2 protein induces apoptosis in infected cells.

Erik Procko, Geoffrey Y Berguig, Betty W Shen, Yifan Song, Shani Frayo, Anthony J Convertine, Daciana Margineantu, Garrett Booth, Bruno E Correia, Yuanhua Cheng and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 1 pooled it
7.3field-weighted citation impact, top 2% 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

78 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.

  1. Pooled it
  2. De Novo-Designed Bifunctional Proteins for Targeted Protein Degradation.Journal of the American Chemical Society · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. A Complementarity-Based Approach to De Novo Binder Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  8. Article
  9. Computational Protein Design - Where it goes?Current medicinal chemistry · 2024
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Tailorable Tetrahelical Bundles as a Toolkit for Redox Studies.The journal of physical chemistry. B · 2022
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Protein Assembly by Design.Chemical reviews · 2021
    Review
  20. Article

18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 1 country.

Erik Procko *Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Geoffrey Y Berguig *Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Betty W ShenFred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Yifan SongDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Shani FrayoFred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Anthony J ConvertineDepartment of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Daciana MargineantuFred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Garrett BoothFred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Bruno E CorreiaThe Scripps Research Institute, La Jolla, CA 92037, USA.
Yuanhua ChengDepartment of Bioengineering, University of Washington, Seattle, WA 98195, USA.
William R SchiefThe Scripps Research Institute, La Jolla, CA 92037, USA.
David M HockenberyFred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Oliver W PressFred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Barry L StoddardFred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Patrick S StaytonDepartment of Bioengineering, University of Washington, Seattle, WA 98195, USA.
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Fred Hutch Cancer Center · USUniversity of Washington · USScripps Research Institute · USHoward Hughes Medical Institute · US

Funding

TrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI MACCOSS, MICHAEL · 2012 to 2021
$20.7M
Radioimmunotherapy Combinations for B-cell MalignancyR01CA076287 · NCI · UNIVERSITY OF WASHINGTON · PI GREEN, DAMIAN J. · 1998 to 2025
$8.1M
Structure, function &engineering of nuclease catalystsR01GM049857 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STODDARD, BARRY L. · 1994 to 2014
$4.2M
CD38 Pretargeted Radioimmunotherapy for MyelomaR01CA154897 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GREEN, DAMIAN J. · 2011 to 2015
$1.8M
Intracellular delivery of proapoptotic peptide drugs for the treatment of cancerR21EB014572 · NIBIB · UNIVERSITY OF WASHINGTON · PI STAYTON, PATRICK S. · 2012 to 2013
$450k
Howard Hughes Medical InstituteNCI NIH HHS R01 CA076287NCI NIH HHS R01CA076287NCI NIH HHS R01 CA154897NCI NIH HHS R01CA154897NIBIB NIH HHS R21 EB014572NIBIB NIH HHS R21EB014572NIGMS NIH HHS P41 GM103533NIGMS NIH HHS P41GM103533NIGMS NIH HHS R01 GM049857NIGMS NIH HHS R01GM49857
6 · The paper itself

Abstract

Because apoptosis of infected cells can limit virus production and spread, some viruses have co-opted prosurvival genes from the host. This includes the Epstein-Barr virus (EBV) gene BHRF1, a homolog of human Bcl-2 proteins that block apoptosis and are associated with cancer. Computational design and experimental optimization were used to generate a novel protein called BINDI that binds BHRF1 with picomolar affinity. BINDI recognizes the hydrophobic cleft of BHRF1 in a manner similar to other Bcl-2 protein interactions but makes many additional contacts to achieve exceptional affinity and specificity. BINDI induces apoptosis in EBV-infected cancer lines, and when delivered with an antibody-targeted intracellular delivery carrier, BINDI suppressed tumor growth and extended survival in a xenograft disease model of EBV-positive human lymphoma. High-specificity-designed proteins that selectively kill target cells may provide an advantage over the toxic compounds used in current generation antibody-drug conjugates.

Indexed as

Protein EngineeringAmino Acid SequenceAnimalsApoptosisComputational BiologyCrystallography, X-RayEpstein-Barr Virus InfectionsHerpesvirus 4, HumanHeterograftsHumansLymphoma, B-CellMiceModels, MolecularMolecular Sequence DataNeoplasm TransplantationProteinsBHRF1 protein, Human herpesvirus 4BINDI proteinProteinsViral Proteins

Identifiers

PMID24949974
PMCPMC4079535
OpenAlexW2057706355

What OpenQuestion holds

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LicenceTDM
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.