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dc.contributor.authorTurnbull, Jordan
dc.contributor.authorWright, Bernice
dc.contributor.authorGreen, Nicola K
dc.contributor.authorTarrant, Richard
dc.contributor.authorRoberts, Iwan
dc.contributor.authorHardick, Oliver
dc.contributor.authorBracewell, Daniel G
dc.date.accessioned2019-08-13T09:16:26Z
dc.date.available2019-08-13T09:16:26Z
dc.date.issued2019-03-28
dc.identifier.citationTurnbull, J., Wright, B., Green, N. K., Tarrant, R., Roberts, I., Hardick, O. and Bracewell, D. G. (2019) Adenovirus 5 recovery using nanofiber ion‐exchange adsorbents, Biotechnology and Bioengineering, 116(7), pp. 1698-1709.en
dc.identifier.issn0006-3592en
dc.identifier.doi10.1002/bit.26972en
dc.identifier.urihttp://hdl.handle.net/2436/622643
dc.description.abstractViral vectors such as adenovirus have successful applications in vaccines and gene therapy but the manufacture of the high‐quality virus remains a challenge. It is desirable to use the adsorption‐based chromatographic separations that so effectively underpin the therapeutic protein manufacture. However fundamental differences in the size and stability of this class of product mean it is necessary to revisit the design of sorbent's morphology and surface chemistry. In this study, the behaviour of a cellulose nanofiber ion‐exchange sorbent derivatised with quaternary amine ligands at defined densities is characterised to address this. This material was selected as it has a large accessible surface area for viral particles and rapid process times. Initially, the impact of surface chemistry on infective product recovery using low (440 µmol/g), medium (750 µmol/g), and high (1029 µmol/g) ligand densities is studied. At higher densities product stability is reduced, this effect increased with prolonged adsorption durations of 24 min with just ~10% loss at low ligand density versus ~50% at high. This could be mitigated by using a high flow rate to reduce the cycle time to ~1 min. Next, the impact of ligand density on the separation's resolution was evaluated. Key to understanding virus quality is the virus particle: infectious virus particle ratio. It was found this parameter could be manipulated using ligand density and elution strategy. Together this provides a basis for viral vector separations that allows for their typically low titres and labile nature by using high liquid velocity to minimise both load and on‐column times while separating key product and process‐related impurities.en
dc.description.sponsorshipThis study was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) grant EP/L01520X/1, and Puridify (now part of GE Healthcare), in conjunction with grant EP/N013395/1.en
dc.formatapplication/PDFen
dc.languageen
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttps://onlinelibrary.wiley.com/doi/full/10.1002/bit.26972en
dc.subjectanion exchange chromatographyen
dc.subjectdownstream processingen
dc.subjectnanofibersen
dc.subjectviral vectorsen
dc.titleAdenovirus 5 recovery using nanofiber ion‐exchange adsorbentsen
dc.typeJournal articleen
dc.identifier.eissn1097-0290
dc.identifier.journalBiotechnology and Bioengineeringen
dc.date.updated2019-08-12T13:15:05Z
dc.date.accepted2019-03-14
rioxxterms.funderEPSRCen
rioxxterms.identifier.projectEP/N013395/1en
rioxxterms.identifier.projectEP/L01520X/1en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.licenseref.startdate2020-03-28en
dc.source.volume116
dc.source.issue7
dc.source.beginpage1698
dc.source.endpage1709
dc.description.versionPublished version
refterms.dateFCD2019-08-13T09:15:30Z
refterms.versionFCDAM


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