Evidence map›Paper›PMID 29382384›Full record

ArticleBMC systems biology2018

Modeling the therapeutic efficacy of NFκB synthetic decoy oligodeoxynucleotides (ODNs).

Zhipeng Wang, Davit A Potoyan, Peter G Wolynes

Abstract read
In one paragraph

Article in BMC systems biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. 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

3 authors.

Zhipeng WangCenter for Theoretical Biological Physics, Rice University, Houston, 77005, TX, USA.ORCID 0000-0001-5703-5560
Davit A PotoyanCenter for Theoretical Biological Physics, Rice University, Houston, 77005, TX, USA.
Peter G WolynesCenter for Theoretical Biological Physics, Rice University, Houston, 77005, TX, USA. pwolynes@rice.edu.

Funding

STRUCTURE AND STABILITY OF IKB/NF-KB COMPLEXESP01GM071862 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOMIVES, ELIZABETH A. · 2006 to 2016
$14.9M
NIGMS NIH HHS P01 GM071862
6 · The paper itself

Abstract

backgroundTransfection of NF κB synthetic decoy Oligodeoxynucleotides (ODNs) has been proposed as a promising therapeutic strategy for a variety of diseases arising from constitutive activation of the eukaryotic transcription factor NF κB. The decoy approach faces some limitations under physiological conditions notably nuclease-induced degradation.

resultsIn this work, we show how a systems pharmacology model of NF κB regulatory networks displaying oscillatory temporal dynamics, can be used to predict quantitatively the dependence of therapeutic efficacy of NF κB synthetic decoy ODNs on dose, unbinding kinetic rates and nuclease-induced degradation rates. Both deterministic mass action simulations and stochastic simulations of the systems biology model show that the therapeutic efficacy of synthetic decoy ODNs is inversely correlated with unbinding kinetic rates, nuclease-induced degradation rates and molecular stripping rates, but is positively correlated with dose. We show that the temporal coherence of the stochastic dynamics of NF κB regulatory networks is most sensitive to adding NF κB synthetic decoy ODNs having unbinding time-scales that are in-resonance with the time-scale of the limit cycle of the network.

conclusionsThe pharmacokinetics/pharmacodynamics (PK/PD) predicted by the systems-level model should provide quantitative guidance for in-depth translational research of optimizing the thermodynamics/kinetic properties of synthetic decoy ODNs.

Indexed as

Models, BiologicalDeoxyribonucleasesDose-Response Relationship, DrugGene Regulatory NetworksKineticsOligodeoxyribonucleotidesStochastic ProcessesDeoxyribonucleasesNF-kappaB decoyOligodeoxyribonucleotidesNF κB synthetic decoy ODNsSystems biologySystems pharmacologyTherapeutic efficacy

Identifiers

PMID29382384
PMCPMC5791368

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.