title: Kinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein A-I.
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.
authors: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Navarra, Spain.
authors: Zinnia Patricia
authors: ZP
authors: Parra-Guillen
authors: Jessica
authors: J
authors: Fioravanti
authors: Jose
authors: J
authors: Medina-Echeverz
authors: Celia
authors: C
authors: Gomar
authors: Nuria
authors: N
authors: Ardaiz
authors: Iñaki F
authors: IF
authors: Troconiz
authors: Pedro
authors: P
authors: Berraondo
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D003198:Computer Simulation; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D011993:Recombinant Fusion Proteins / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D016898:Interferon-alpha; D011993:Recombinant Fusion Proteins