Cargando…
Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression
Oncolytic viruses (OVs) promote the anti-tumor immune response as their replication, and the subsequent lysis of tumor cells, triggers the activation of immune-sensing pathways. Arming OVs by expressing transgenes with the potential to promote immune cell recruitment and activation is an attractive...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018389/ https://www.ncbi.nlm.nih.gov/pubmed/36938543 http://dx.doi.org/10.1016/j.omto.2023.02.005 |
_version_ | 1784907800374149120 |
---|---|
author | Bryant, Jeffrey D. Lee, Jennifer S. De Almeida, Ana Jacques, Judy Chang, Ching-Hung Fassler, William Quéva, Christophe Lerner, Lorena Kennedy, Edward M. |
author_facet | Bryant, Jeffrey D. Lee, Jennifer S. De Almeida, Ana Jacques, Judy Chang, Ching-Hung Fassler, William Quéva, Christophe Lerner, Lorena Kennedy, Edward M. |
author_sort | Bryant, Jeffrey D. |
collection | PubMed |
description | Oncolytic viruses (OVs) promote the anti-tumor immune response as their replication, and the subsequent lysis of tumor cells, triggers the activation of immune-sensing pathways. Arming OVs by expressing transgenes with the potential to promote immune cell recruitment and activation is an attractive strategy to enhance OVs’ therapeutic benefit. For picornaviruses, a family of OVs with clinical experience, the expression of a transgene is limited by multiple factors: genome physical packaging limits, high rates of recombination, and viral-mediated inhibition of transgene secretion. Here, we evaluated strategies for arming Seneca Valley virus (SVV) with relevant immunomodulatory transgenes. Specificially in the contex of arming SVV, we evaluated transgene maximum size and stabiltity, transgene secretion, and the impact of transgene inclusion on viral fitness. We find that SVV is not capable of expressing secreted payloads and has a transgene packaging capacity of ∼10% of viral genome size. To enable transgene expression, we developed SVV replicons with greater transgene size capacity and secretion capabilities. SVV replicons can be packaged in trans by virus in co-infected cells to express immunomodulatory transgenes in surrounding cells, thus providing a means to enhance the potential of this therapeutic to augment the anti-tumor immune response. |
format | Online Article Text |
id | pubmed-10018389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-100183892023-03-17 Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression Bryant, Jeffrey D. Lee, Jennifer S. De Almeida, Ana Jacques, Judy Chang, Ching-Hung Fassler, William Quéva, Christophe Lerner, Lorena Kennedy, Edward M. Mol Ther Oncolytics Original Article Oncolytic viruses (OVs) promote the anti-tumor immune response as their replication, and the subsequent lysis of tumor cells, triggers the activation of immune-sensing pathways. Arming OVs by expressing transgenes with the potential to promote immune cell recruitment and activation is an attractive strategy to enhance OVs’ therapeutic benefit. For picornaviruses, a family of OVs with clinical experience, the expression of a transgene is limited by multiple factors: genome physical packaging limits, high rates of recombination, and viral-mediated inhibition of transgene secretion. Here, we evaluated strategies for arming Seneca Valley virus (SVV) with relevant immunomodulatory transgenes. Specificially in the contex of arming SVV, we evaluated transgene maximum size and stabiltity, transgene secretion, and the impact of transgene inclusion on viral fitness. We find that SVV is not capable of expressing secreted payloads and has a transgene packaging capacity of ∼10% of viral genome size. To enable transgene expression, we developed SVV replicons with greater transgene size capacity and secretion capabilities. SVV replicons can be packaged in trans by virus in co-infected cells to express immunomodulatory transgenes in surrounding cells, thus providing a means to enhance the potential of this therapeutic to augment the anti-tumor immune response. American Society of Gene & Cell Therapy 2023-02-16 /pmc/articles/PMC10018389/ /pubmed/36938543 http://dx.doi.org/10.1016/j.omto.2023.02.005 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Bryant, Jeffrey D. Lee, Jennifer S. De Almeida, Ana Jacques, Judy Chang, Ching-Hung Fassler, William Quéva, Christophe Lerner, Lorena Kennedy, Edward M. Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression |
title | Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression |
title_full | Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression |
title_fullStr | Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression |
title_full_unstemmed | Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression |
title_short | Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression |
title_sort | seneca valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018389/ https://www.ncbi.nlm.nih.gov/pubmed/36938543 http://dx.doi.org/10.1016/j.omto.2023.02.005 |
work_keys_str_mv | AT bryantjeffreyd senecavalleyvirusrepliconsarepackagedintransandhavethecapacitytoovercomethelimitationsofviraltransgeneexpression AT leejennifers senecavalleyvirusrepliconsarepackagedintransandhavethecapacitytoovercomethelimitationsofviraltransgeneexpression AT dealmeidaana senecavalleyvirusrepliconsarepackagedintransandhavethecapacitytoovercomethelimitationsofviraltransgeneexpression AT jacquesjudy senecavalleyvirusrepliconsarepackagedintransandhavethecapacitytoovercomethelimitationsofviraltransgeneexpression AT changchinghung senecavalleyvirusrepliconsarepackagedintransandhavethecapacitytoovercomethelimitationsofviraltransgeneexpression AT fasslerwilliam senecavalleyvirusrepliconsarepackagedintransandhavethecapacitytoovercomethelimitationsofviraltransgeneexpression AT quevachristophe senecavalleyvirusrepliconsarepackagedintransandhavethecapacitytoovercomethelimitationsofviraltransgeneexpression AT lernerlorena senecavalleyvirusrepliconsarepackagedintransandhavethecapacitytoovercomethelimitationsofviraltransgeneexpression AT kennedyedwardm senecavalleyvirusrepliconsarepackagedintransandhavethecapacitytoovercomethelimitationsofviraltransgeneexpression |