Anion-exchange membrane chromatography for purification of rotavirus-like particles

Vicente, Tiago; Sousa, Marcos F. Q.; Peixoto, Cristina; Mota, José P. B.; Alves, Paula M.; Carrondo, Manuel J.T.

doi:10.1016/j.memsci.2007.12.021

Cited by 82 publications

(50 citation statements)

References 31 publications

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“…When membrane is used as a matrix, however, the interaction of the binding sites and the target molecules occurs in convective flow-through pores. 40 As a result, membrane chromatography is particularly useful for purification of large molecules with low diffusivities, and therefore, is increasingly explored to replace conventional chromatographic resins for VLP purification. 41 Other membrane separation methods developed for non-biological nanoparticles also have potential applications for VLP purification.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

Geminiviral vectors based on bean yellow dwarf virus for production of vaccine antigens and monoclonal antibodies in plants

et al. 2011

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Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

Geminiviral vectors based on bean yellow dwarf virus for production of vaccine antigens and monoclonal antibodies in plants

et al. 2011

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“…Still, many downstream processing teams in the industry and academia frequently resort to ultracentrifugation-based purification steps to generate their viral stocks; these are typically costly, non-cGMP amenable and not easily scalable. To circumvent this, ion-exchange (IEX) chromatography, which is scalable and cGMP compliant, is becoming the process of choice for the recovery of not only recombinant proteins or vaccines but also viral vectors (Okada et al, 2009;Opitz et al, 2007;Peixoto et al, 2008;Rodrigues et al, 2006;Vicente et al, 2008Vicente et al, , 2009. The issue then is to find an efficient means for the optimization of this preferred process.…”

Section: Introductionmentioning

confidence: 99%

“…To complement these analytical tools, good modeling tools are also required for a more sound design of the actual purification process. For instance, the steric mass action (SMA) model of ion exchange (Brooks and Cramer, 1992) has been employed in concert with a standard chromatographic column model to simulate and predict with reasonable accuracy VLP-binding and elution in anion-exchange membrane chromatography (AEXmc; Vicente et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Impact of ligand density on the optimization of ion‐exchange membrane chromatography for viral vector purification

Vicente

Faber

Alves

et al. 2011

Biotech & Bioengineering

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The effect of ligand density on anion-exchange membrane chromatography (AEXmc) for the purification of recombinant baculoviruses (rBVs), potential viral vectors in clinical applications, is studied by surface plasmon resonance on customized AEX surfaces and gradient elution experiments on Sartobind D membrane prototypes with different diethylamine ligand densities, complemented by dynamic light scattering analysis for estimation of the hydrodynamic particle size of the various biologics. A chromatographic-column model based on the steric mass action model of ion exchange is employed to analyze the gradient-elution AEXmc experiments, extrapolate the results to other operating conditions, and provide directions for process improvement. Although counterintuitively, the experimental evidence provided in this study shows that the lowering of ligand density is beneficial for rBV purification by AEXmc in bind-and-elute-mode, because it decreases the residual concentrations of host cell protein, dsDNA, and non-infective rBVs in the eluted product cut, and increases the overall yield by roughly 20% over current standard values. Overall, we present a case study on how rational design can streamline downstream process development.

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“…Porous membrane adsorbers have been successfully applied in lab-scale [1] and large-scale antibody production for trace contaminant removal and virus clearance [2,3]. To date, much research for improvement of membrane adsorber separation performance has been focused on materials such as base membranes that are more suitable and efficient [4,5], improved surface chemistries [6][7][8][9], on transport mechanisms [10][11][12][13][14][15], as well as on correlations between materials and transport mechanisms [16]. Some particularly effective improvements have been achieved by novel membrane module designs to optimize flow distribution of membrane devices on a lab- [17][18][19][20][21] and production-scale [22,23].…”

Section: Introductionmentioning

confidence: 99%

“…In these approaches, dead volumes in membrane chromatography systems are traditionally modeled by one plug flow reactor (PFR) and one continuous stirred tank reactor (CSTR) in series [10,11], or by lumping the overall peak broadening and tailing effects into a fixed volume of a mixing cell [15]. However, this setup could systematically not explain specific features of chromatograms measured by the current authors with different porous membrane adsorbers [7,25,26].…”

Section: Introductionmentioning

confidence: 99%

Model Based Quantification of Internal Flow Distributions from Breakthrough Curves of Flat Sheet Membrane Chromatography Modules

2010

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A novel model for quantifying radial flow distributions in flat sheet membrane chromatography modules under non-binding conditions is presented and applied for the practical analysis of two modules. The proposed model partitions the total void volume of the chromatography module into zones that are considered homogeneous with respect to flow velocity. The corresponding solute concentrations are time variant, but also spatially homogeneous within each zone. The model is mathematically represented and analytically solved as a network of continuously stirred tank reactors (CSTR). An additional plug flow reactor (PFR) is connected in series with the CSTR network in order to account for a time-lag that is not associated with the system dispersion. The capability of the model to describe experimental breakthrough data is compared to the frequently applied standard model for extra-membrane system dispersion, which consists of a single CSTR in series with a PFR. Non-binding conditions are deliberately chosen for studying the impact of module geometries on breakthrough curves separately from chromatographic membrane performance. The commercial CIM module and a custom designed cell (Scell) are studied with acetone and lysozyme as test tracers at varied flow rates and for various membrane pore sizes under non-binding conditions. In all studied cases, the proposed model fits the measured breakthrough curves better than the standard model. Moreover, the minimal number of radial flow zones that are required to accurately describe observed breakthrough curves and the estimated flow fractions through these zones provide valuable information for the analysis and optimization of internal module designs.

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Anion-exchange membrane chromatography for purification of rotavirus-like particles

Cited by 82 publications

References 31 publications

Geminiviral vectors based on bean yellow dwarf virus for production of vaccine antigens and monoclonal antibodies in plants

Geminiviral vectors based on bean yellow dwarf virus for production of vaccine antigens and monoclonal antibodies in plants

Impact of ligand density on the optimization of ion‐exchange membrane chromatography for viral vector purification

Model Based Quantification of Internal Flow Distributions from Breakthrough Curves of Flat Sheet Membrane Chromatography Modules

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