Kinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein A-I.

Interferon alpha linked to apolipoprotein A-I has been recently proposed as an improved interferon-based therapy. In the present study, we aimed to develop a computational model to gain further insight into the in vivo behaviour of this new fusion protein. In order to facilitate in vivo evaluation o...

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Autores principales:	Zinnia Patricia Parra-Guillen, Jessica Fioravanti, Jose Medina-Echeverz, Celia Gomar, Nuria Ardaiz, Iñaki F Troconiz, Pedro Berraondo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b9c8a9547a1a4ebb8f25d94d2779164c
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spelling	oai:doaj.org-article:b9c8a9547a1a4ebb8f25d94d2779164c2021-11-18T07:10:35ZKinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein A-I.1932-620310.1371/journal.pone.0042100https://doaj.org/article/b9c8a9547a1a4ebb8f25d94d2779164c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22848716/?tool=EBIhttps://doaj.org/toc/1932-6203Interferon alpha linked to apolipoprotein A-I has been recently proposed as an improved interferon-based therapy. In the present study, we aimed to develop a computational model to gain further insight into the in vivo behaviour of this new fusion protein. In order to facilitate in vivo evaluation of interferon and the fusion protein without altering their biological properties, green fluorescent protein was incorporated into their structures. Kinetic and dynamic behaviour of both compounds was successfully described after plasmid hydrodynamic administration and in situ synthesis of the studied proteins. Results from the modelling exercise showed that apolipoprotein A-I conferred a modified kinetic behaviour, varying molecule distribution and prolonging half-life without altering liver dynamic performance. However, differences in the gene expression activity were observed at brain level between both compounds. Those differences could be explained by modifications in the dynamic, but also in the biodistribution properties, which would be worth evaluating in future experiments. Therefore, the modelling approach provided a global comprehension of a complex system and allowed us to compare the in vivo behaviour of both compounds and to identify critical aspects that might be important to understand the system better and suggests a need for new model-based experiments.Zinnia Patricia Parra-GuillenJessica FioravantiJose Medina-EcheverzCelia GomarNuria ArdaizIñaki F TroconizPedro BerraondoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e42100 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zinnia Patricia Parra-Guillen Jessica Fioravanti Jose Medina-Echeverz Celia Gomar Nuria Ardaiz Iñaki F Troconiz Pedro Berraondo Kinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein A-I.
description	Interferon alpha linked to apolipoprotein A-I has been recently proposed as an improved interferon-based therapy. In the present study, we aimed to develop a computational model to gain further insight into the in vivo behaviour of this new fusion protein. In order to facilitate in vivo evaluation of interferon and the fusion protein without altering their biological properties, green fluorescent protein was incorporated into their structures. Kinetic and dynamic behaviour of both compounds was successfully described after plasmid hydrodynamic administration and in situ synthesis of the studied proteins. Results from the modelling exercise showed that apolipoprotein A-I conferred a modified kinetic behaviour, varying molecule distribution and prolonging half-life without altering liver dynamic performance. However, differences in the gene expression activity were observed at brain level between both compounds. Those differences could be explained by modifications in the dynamic, but also in the biodistribution properties, which would be worth evaluating in future experiments. Therefore, the modelling approach provided a global comprehension of a complex system and allowed us to compare the in vivo behaviour of both compounds and to identify critical aspects that might be important to understand the system better and suggests a need for new model-based experiments.
format	article
author	Zinnia Patricia Parra-Guillen Jessica Fioravanti Jose Medina-Echeverz Celia Gomar Nuria Ardaiz Iñaki F Troconiz Pedro Berraondo
author_facet	Zinnia Patricia Parra-Guillen Jessica Fioravanti Jose Medina-Echeverz Celia Gomar Nuria Ardaiz Iñaki F Troconiz Pedro Berraondo
author_sort	Zinnia Patricia Parra-Guillen
title	Kinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein A-I.
title_short	Kinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein A-I.
title_full	Kinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein A-I.
title_fullStr	Kinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein A-I.
title_full_unstemmed	Kinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein A-I.
title_sort	kinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein a-i.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/b9c8a9547a1a4ebb8f25d94d2779164c
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Kinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein A-I.

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