Production and Purification of High-Titer Newcastle Disease Virus for Use in Preclinical Mouse Models of Cancer
Newcastle disease virus (NDV) is a single-stranded, negative-sense RNA virus in the Paramyxoviridae family. Although primarily an avian pathogen, NDV is a potent oncolytic virus that has been shown to be safe and effective in a variety of preclinical cancer models and human clinical trials. To produ...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-06-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050117301158 |
| _version_ | 1818696076523208704 |
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| author | Lisa A. Santry Thomas M. McAusland Leonardo Susta Geoffrey A. Wood Pierre P. Major Jim J. Petrik Byram W. Bridle Sarah K. Wootton |
| author_facet | Lisa A. Santry Thomas M. McAusland Leonardo Susta Geoffrey A. Wood Pierre P. Major Jim J. Petrik Byram W. Bridle Sarah K. Wootton |
| author_sort | Lisa A. Santry |
| collection | DOAJ |
| description | Newcastle disease virus (NDV) is a single-stranded, negative-sense RNA virus in the Paramyxoviridae family. Although primarily an avian pathogen, NDV is a potent oncolytic virus that has been shown to be safe and effective in a variety of preclinical cancer models and human clinical trials. To produce virus for oncolytic trials, NDV is commonly amplified in embryonated chicken eggs and purified from the allantoic fluid. Conventional methods for purifying virus from allantoic fluid often result in relatively low-titer preparations containing high levels of impurities, including immunogenic chicken host cell proteins from allantoic fluid. However, large quantities of virus need to be delivered intravenously to administer oncolytic NDV systemically to mice. This route of administration requires virus preparations that are both highly concentrated (to enable delivery of small volumes) and highly pure (to limit toxic effects from contaminants). Given the accumulation of promising preclinical and clinical data demonstrating the efficacy of NDV as an oncolytic agent, strategies for increasing the titer and purity of NDV preparations are sorely needed to allow for effective intravenous administration in mice. Here, we describe an optimized protocol for the rescue, production, and purification of high-titer in vivo-grade NDV for preclinical studies in mouse models. Keywords: Newcastle disease virus, oncolytic virus, tangential flow filtration, preclinical grade, intravenous, allantoic fluid |
| first_indexed | 2024-12-17T13:55:37Z |
| format | Article |
| id | doaj.art-3b2b5b0f2d43414d94bc1fcdec5c2f84 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-17T13:55:37Z |
| publishDate | 2018-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-3b2b5b0f2d43414d94bc1fcdec5c2f842022-12-21T21:45:56ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012018-06-019181191Production and Purification of High-Titer Newcastle Disease Virus for Use in Preclinical Mouse Models of CancerLisa A. Santry0Thomas M. McAusland1Leonardo Susta2Geoffrey A. Wood3Pierre P. Major4Jim J. Petrik5Byram W. Bridle6Sarah K. Wootton7Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, CanadaJuravinski Cancer Centre, 699 Concession Street, Hamilton, ON L8V 5C2, CanadaDepartment of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada; Corresponding author: Sarah K. Wootton, Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada.Newcastle disease virus (NDV) is a single-stranded, negative-sense RNA virus in the Paramyxoviridae family. Although primarily an avian pathogen, NDV is a potent oncolytic virus that has been shown to be safe and effective in a variety of preclinical cancer models and human clinical trials. To produce virus for oncolytic trials, NDV is commonly amplified in embryonated chicken eggs and purified from the allantoic fluid. Conventional methods for purifying virus from allantoic fluid often result in relatively low-titer preparations containing high levels of impurities, including immunogenic chicken host cell proteins from allantoic fluid. However, large quantities of virus need to be delivered intravenously to administer oncolytic NDV systemically to mice. This route of administration requires virus preparations that are both highly concentrated (to enable delivery of small volumes) and highly pure (to limit toxic effects from contaminants). Given the accumulation of promising preclinical and clinical data demonstrating the efficacy of NDV as an oncolytic agent, strategies for increasing the titer and purity of NDV preparations are sorely needed to allow for effective intravenous administration in mice. Here, we describe an optimized protocol for the rescue, production, and purification of high-titer in vivo-grade NDV for preclinical studies in mouse models. Keywords: Newcastle disease virus, oncolytic virus, tangential flow filtration, preclinical grade, intravenous, allantoic fluidhttp://www.sciencedirect.com/science/article/pii/S2329050117301158 |
| spellingShingle | Lisa A. Santry Thomas M. McAusland Leonardo Susta Geoffrey A. Wood Pierre P. Major Jim J. Petrik Byram W. Bridle Sarah K. Wootton Production and Purification of High-Titer Newcastle Disease Virus for Use in Preclinical Mouse Models of Cancer Molecular Therapy: Methods & Clinical Development |
| title | Production and Purification of High-Titer Newcastle Disease Virus for Use in Preclinical Mouse Models of Cancer |
| title_full | Production and Purification of High-Titer Newcastle Disease Virus for Use in Preclinical Mouse Models of Cancer |
| title_fullStr | Production and Purification of High-Titer Newcastle Disease Virus for Use in Preclinical Mouse Models of Cancer |
| title_full_unstemmed | Production and Purification of High-Titer Newcastle Disease Virus for Use in Preclinical Mouse Models of Cancer |
| title_short | Production and Purification of High-Titer Newcastle Disease Virus for Use in Preclinical Mouse Models of Cancer |
| title_sort | production and purification of high titer newcastle disease virus for use in preclinical mouse models of cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2329050117301158 |
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