A simple macroscopic model for the diffusion and adsorption kinetics of r-Adenovirus

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DOIResolve DOI: http://doi.org/10.1002/bit.21340
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TypeArticle
Journal titleBiotechnology and Bioengineering
Volume98
Issue1
Pages239251; # of pages: 13
SubjectAdsorption; bio; biotechnology; cells; culture media; kinetics; recombinant adenovirus; 293S cells; virus diffusion; virus adsorption; kinetic modeling; adsorption isotherm
AbstractThe diffusion of viruses toward cells is a limiting step of the infection process. To be modeled correctly, this step must be evaluated in combination with the adsorption of the virus to the cell surface, which is a rapid but reversible step. In this paper, the recombinant adenovirus (rAd) diffusion and its adsorption to 293S cells in suspension were both measured and modeled. First, equilibrium experiments permitted to determine the number of receptors on the surface of 293S (RT=3,500 cell⁻¹) and the association constant (KA=1.9×10¹¹M⁻¹) for rAd on these cells based on a simple monovalent adsorption model. Nonspecific binding of the virus to the cell surface was not found to be significant. Second, total virus particle degradation rates between 5.2×10⁻³ and 4.0×10⁻² min⁻¹ were measured at 37°C in culture medium, but no significant virus degradation was observed at 4°C. Third, free viral particle disappearance rates from a mixed suspension of virus and cells were measured at different virus concentrations. Experimental data were compared to a phenomenological dynamic model comprising both the diffusion and the adsorption steps. The diffusion to adsorption ratio, a fitted parameter, confirmed that the contact process of a virus with a cell is indeed diffusion controlled. However, the characteristic diffusion time constants obtained, based on a reversible adsorption model, were eightfolds smaller than those reported in the literature, based on diffusion models that assume irreversible adsorption.
Publication date
LanguageEnglish
AffiliationNRC Biotechnology Research Institute; National Research Council Canada
Peer reviewedNo
NRC number47803
47803
NPARC number3540116
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Record identifier922b211a-b268-4af4-9665-33c7548f2194
Record created2009-03-01
Record modified2016-05-09
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