Evidence map›Paper›PMID 27633441›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016

Intracellular Delivery of Anti-pPKCθ (Thr538) via Protein Transduction Domain Mimics for Immunomodulation.

E Ilker Ozay, Gabriela Gonzalez-Perez, Joe A Torres, Jyothi Vijayaraghavan, Rebecca Lawlor, Heather L Sherman, Daniel T Garrigan, Amy S Burnside, Barbara A Osborne, Gregory N Tew and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

16 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Targeting the Inside of Cells with Biologicals: Chemicals as a Delivery Strategy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
  6. Article
  7. Article
  8. Protein Kinase C Theta Modulates PCMT1 through hnRNPL to Regulate FOXP3 Stability in Regulatory T Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Article
  9. Article
  10. Article
  11. Review
  12. Article
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  14. Review
  15. Article
  16. 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

11 authors at 2 institutions in 1 country.

E Ilker OzayProgram in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
Gabriela Gonzalez-PerezDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Columbia University, New York, New York, USA.
Joe A TorresProgram in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
Jyothi VijayaraghavanDepartment of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
Rebecca LawlorDepartment of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
Heather L ShermanProgram in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
Daniel T GarriganDepartment of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
Amy S BurnsideInstitute for Applied Life Sciences, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
Barbara A OsborneProgram in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
Gregory N TewProgram in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
Lisa M MinterProgram in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
University of Massachusetts Amherst · USColumbia University · US

Funding

Targeting y-secretase in GVHDP01CA166009 · NCI · UNIVERSITY OF MASSACHUSETTS AMHERST · PI OSBORNE, BARBARA A · 2013 to 2017
$4.9M
Biotechnology Training Program in Applied Life SciencesT32GM135096 · NIGMS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI Jeanne Ann Hardy, Ashish A. Kulkarni · 2020 to 2026
$3.9M
Cellular Engineering Biotechnology Training ProgramT32GM108556 · NIGMS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI HARDY, JEANNE ANN, PEYTON, SHELLY R. · 2015 to 2019
$766k
NCI NIH HHS P01 CA166009NIGMS NIH HHS T32 GM108556NIGMS NIH HHS T32 GM135096
6 · The paper itself

Abstract

Targeting cellular proteins with antibodies, to better understand cellular signaling pathways in the context of disease modulation, is a fast-growing area of investigation. Humanized antibodies are increasingly gaining attention for their therapeutic potential, but the collection of cellular targets is limited to those secreted from cells or expressed on the cell surface. This approach leaves a wealth of intracellular proteins unexplored as putative targets for antibody binding. Protein kinase Cθ (PKCθ) is essential to T cell activation, proliferation, and differentiation, and its phosphorylation at specific residues is required for its activity. Here we report on the design, synthesis, and characterization of a protein transduction domain mimic capable of efficiently delivering an antibody against phosphorylated PKCθ (Thr538) into human peripheral mononuclear blood cells and altering expression of downstream indicators of T cell activation and differentiation. We used a humanized, lymphocyte transfer model of graft-versus-host disease, to evaluate the durability of protein transduction domain mimic:Anti-pPKCθ modulation, when delivered into human peripheral mononuclear blood cells ex vivo. We demonstrate that protein transduction domain mimic:Antibody complexes can be readily introduced with high efficacy into hard-to-transfect human peripheral mononuclear blood cells, eliciting a biological response sufficient to alter disease progression. Thus, protein transduction domain mimic:Antibody delivery may represent an efficient ex vivo approach to manipulating cellular responses by targeting intracellular proteins.

Indexed as

AnimalsAntibodies, Monoclonal, HumanizedCell DifferentiationCell-Penetrating PeptidesCell ProliferationGraft vs Host DiseaseHumansImmunomodulationIsoenzymesLeukocytes, MononuclearLymphocyte ActivationMicePhosphorylationProtein Kinase CProtein Kinase C-thetaSignal TransductionAntibodies, Monoclonal, HumanizedCell-Penetrating PeptidesIsoenzymesPRKCQ protein, humanProtein Kinase CProtein Kinase C-theta

Identifiers

PMID27633441
PMCPMC5167783
OpenAlexW2519633838

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.