Show simple item record

dc.contributor.authorWang, Zhipeng
Potoyan, Davit A.
Wolynes, Peter G.
dc.date.accessioned 2018-07-11T17:18:36Z
dc.date.available 2018-07-11T17:18:36Z
dc.date.issued 2018
dc.identifier.citation Wang, Zhipeng, Potoyan, Davit A. and Wolynes, Peter G.. "Modeling the therapeutic efficacy of NFκBsynthetic decoy oligodeoxynucleotides (ODNs)." BMC Systems Biology, 12, (2018) BMC: https://doi.org/10.1186/s12918-018-0525-6.
dc.identifier.urihttps://hdl.handle.net/1911/102383
dc.description.abstract Background: Transfection 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. Results: In 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. Conclusions: The 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.
dc.language.iso eng
dc.publisher BMC
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.title Modeling the therapeutic efficacy of NFκBsynthetic decoy oligodeoxynucleotides (ODNs)
dc.type Journal article
dc.citation.journalTitle BMC Systems Biology
dc.citation.volumeNumber 12
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1186/s12918-018-0525-6
dc.identifier.pmcid PMC5791368
dc.identifier.pmid 29382384
dc.type.publication publisher version
dc.citation.articleNumber 4


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Except where otherwise noted, this item's license is described as This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.