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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
- Source :
- PLoS ONE, Vol 7, Iss 7, p e42100 (2012), Dadun. Depósito Académico Digital de la Universidad de Navarra, instname, ResearcherID, PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- 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.
- Subjects :
- Biodistribution
Apolipoprotein B
Recombinant Fusion Proteins
Science
Immunology
Alpha interferon
Gene Expression
Biological Data Management
Computational biology
Models, Biological
Green fluorescent protein
Molecular Genetics
Mice
In vivo
Interferon
Drug Discovery
Molecular Cell Biology
medicine
Genetics
Animals
Humans
Computer Simulation
Interferon Alpha
Biology
Mice, Inbred BALB C
Multidisciplinary
biology
Apolipoprotein A-I
Systems Biology
HEK 293 cells
Computational Biology
Brain
Interferon-alpha
Fusion protein
Molecular biology
Kinetics
HEK293 Cells
Immune System
biology.protein
Cytokines
Medicine
Female
medicine.drug
Research Article
Biotechnology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....7de35a0fae702d7a5e954c630477a959