Development of a recombinant non-replicating Newcastle disease virus

Newcastle disease virus (NDV) is an avian orthoavulavirus I that causes high morbidity and mortality in birds, depending on the pathotype of the virus. Several clinical studies have shown that NDV is a promising oncolytic virus for cancer therapies, yet its application to clinics is restricted due t...

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Main Authors: Cheow, Pheik-Sheen, Tan, Tiong Kit, Song, Adelene Ai-Lian, Yusoff, Khatijah, Chia, Suet Lin
Format: Article
Published: Taylor and Francis 2024
Online Access:http://psasir.upm.edu.my/id/eprint/114712/
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author Cheow, Pheik-Sheen
Tan, Tiong Kit
Song, Adelene Ai-Lian
Yusoff, Khatijah
Chia, Suet Lin
author_facet Cheow, Pheik-Sheen
Tan, Tiong Kit
Song, Adelene Ai-Lian
Yusoff, Khatijah
Chia, Suet Lin
author_sort Cheow, Pheik-Sheen
building UPM Institutional Repository
collection Online Access
description Newcastle disease virus (NDV) is an avian orthoavulavirus I that causes high morbidity and mortality in birds, depending on the pathotype of the virus. Several clinical studies have shown that NDV is a promising oncolytic virus for cancer therapies, yet its application to clinics is restricted due to the pathogenicity of this virus in poultry. Hence, it is important to produce a recombinant NDV (rNDV) with reduced virulence to make it a fit candidate as an oncolytic virus. In this study, we aimed to produce a rNDV with a truncated ant-igenome via reverse genetics to render it non-replicating (nr). The genes responsible for replication were removed from the NDV genome. The rescued nr-NDV was verified, propagated, and purified from tissue culture medium. The virus failed to propagate in embryonated eggs, confirming its non-replicating property. The virus retained its oncolytic activities similar to that of the replicating rAF-GFP as observed in a cell viability assay when a breast cancer cell line, MCF-7, was treated with the virus. In conclusion, this study has successfully generated a system to produce a non-replicating NDV which can be used as a viral vector for heterologous protein delivery, as a safer alternative compared to the virulent strains as an oncolytic virus. RESEARCH HIGHLIGHTS: Development of nr-NDV. Reverse transfection was applied for the recovery of nr-NDV. Propagation of nr-NDV was done by sub-passaging transfected BSR T7/5 cells. Safety profile was done to prove that the nr-NDV is non-replicating.
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spelling upm-1147122025-01-24T03:02:18Z http://psasir.upm.edu.my/id/eprint/114712/ Development of a recombinant non-replicating Newcastle disease virus Cheow, Pheik-Sheen Tan, Tiong Kit Song, Adelene Ai-Lian Yusoff, Khatijah Chia, Suet Lin Newcastle disease virus (NDV) is an avian orthoavulavirus I that causes high morbidity and mortality in birds, depending on the pathotype of the virus. Several clinical studies have shown that NDV is a promising oncolytic virus for cancer therapies, yet its application to clinics is restricted due to the pathogenicity of this virus in poultry. Hence, it is important to produce a recombinant NDV (rNDV) with reduced virulence to make it a fit candidate as an oncolytic virus. In this study, we aimed to produce a rNDV with a truncated ant-igenome via reverse genetics to render it non-replicating (nr). The genes responsible for replication were removed from the NDV genome. The rescued nr-NDV was verified, propagated, and purified from tissue culture medium. The virus failed to propagate in embryonated eggs, confirming its non-replicating property. The virus retained its oncolytic activities similar to that of the replicating rAF-GFP as observed in a cell viability assay when a breast cancer cell line, MCF-7, was treated with the virus. In conclusion, this study has successfully generated a system to produce a non-replicating NDV which can be used as a viral vector for heterologous protein delivery, as a safer alternative compared to the virulent strains as an oncolytic virus. RESEARCH HIGHLIGHTS: Development of nr-NDV. Reverse transfection was applied for the recovery of nr-NDV. Propagation of nr-NDV was done by sub-passaging transfected BSR T7/5 cells. Safety profile was done to prove that the nr-NDV is non-replicating. Taylor and Francis 2024-09-25 Article PeerReviewed Cheow, Pheik-Sheen and Tan, Tiong Kit and Song, Adelene Ai-Lian and Yusoff, Khatijah and Chia, Suet Lin (2024) Development of a recombinant non-replicating Newcastle disease virus. Avian Pathology, 54 (1). pp. 149-157. ISSN 0307-9457; eISSN: 1465-3338 https://www.tandfonline.com/doi/full/10.1080/03079457.2024.2403412 10.1080/03079457.2024.2403412
spellingShingle Cheow, Pheik-Sheen
Tan, Tiong Kit
Song, Adelene Ai-Lian
Yusoff, Khatijah
Chia, Suet Lin
Development of a recombinant non-replicating Newcastle disease virus
title Development of a recombinant non-replicating Newcastle disease virus
title_full Development of a recombinant non-replicating Newcastle disease virus
title_fullStr Development of a recombinant non-replicating Newcastle disease virus
title_full_unstemmed Development of a recombinant non-replicating Newcastle disease virus
title_short Development of a recombinant non-replicating Newcastle disease virus
title_sort development of a recombinant non-replicating newcastle disease virus
url http://psasir.upm.edu.my/id/eprint/114712/
http://psasir.upm.edu.my/id/eprint/114712/
http://psasir.upm.edu.my/id/eprint/114712/