Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells.

Experimental evolution has been used for various biotechnological applications including protein and microbial cell engineering, but less commonly in the field of oncolytic virotherapy. Here, we sought to adapt a rapidly evolving RNA virus to cells deficient for the tumor suppressor gene p53, a hall...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Raquel Garijo, Pablo Hernández-Alonso, Carmen Rivas, Jean-Simon Diallo, Rafael Sanjuán
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c084da314e344d8193753f27dfe89078
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c084da314e344d8193753f27dfe89078
record_format	dspace
spelling	oai:doaj.org-article:c084da314e344d8193753f27dfe890782021-11-25T06:09:00ZExperimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells.1932-620310.1371/journal.pone.0102365https://doaj.org/article/c084da314e344d8193753f27dfe890782014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25010337/?tool=EBIhttps://doaj.org/toc/1932-6203Experimental evolution has been used for various biotechnological applications including protein and microbial cell engineering, but less commonly in the field of oncolytic virotherapy. Here, we sought to adapt a rapidly evolving RNA virus to cells deficient for the tumor suppressor gene p53, a hallmark of cancer cells. To achieve this goal, we established four independent evolution lines of the vesicular stomatitis virus (VSV) in p53-knockout mouse embryonic fibroblasts (p53-/- MEFs) under conditions favoring the action of natural selection. We found that some evolved viruses showed increased fitness and cytotoxicity in p53-/- cells but not in isogenic p53+/+ cells, indicating gene-specific adaptation. However, full-length sequencing revealed no obvious or previously described genetic changes associated with oncolytic activity. Half-maximal effective dose (EC50) assays in mouse p53-positive colon cancer (CT26) and p53-deficient breast cancer (4T1) cells indicated that the evolved viruses were more effective against 4T1 cells than the parental virus or a reference oncolytic VSV (MΔ51), but showed no increased efficacy against CT26 cells. In vivo assays using 4T1 syngeneic tumor models showed that one of the evolved lines significantly delayed tumor growth compared to mice treated with the parental virus or untreated controls, and was able to induce transient tumor suppression. Our results show that RNA viruses can be specifically adapted typical cancer features such as p53 inactivation, and illustrate the usefulness of experimental evolution for oncolytic virotherapy.Raquel GarijoPablo Hernández-AlonsoCarmen RivasJean-Simon DialloRafael SanjuánPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e102365 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Raquel Garijo Pablo Hernández-Alonso Carmen Rivas Jean-Simon Diallo Rafael Sanjuán Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells.
description	Experimental evolution has been used for various biotechnological applications including protein and microbial cell engineering, but less commonly in the field of oncolytic virotherapy. Here, we sought to adapt a rapidly evolving RNA virus to cells deficient for the tumor suppressor gene p53, a hallmark of cancer cells. To achieve this goal, we established four independent evolution lines of the vesicular stomatitis virus (VSV) in p53-knockout mouse embryonic fibroblasts (p53-/- MEFs) under conditions favoring the action of natural selection. We found that some evolved viruses showed increased fitness and cytotoxicity in p53-/- cells but not in isogenic p53+/+ cells, indicating gene-specific adaptation. However, full-length sequencing revealed no obvious or previously described genetic changes associated with oncolytic activity. Half-maximal effective dose (EC50) assays in mouse p53-positive colon cancer (CT26) and p53-deficient breast cancer (4T1) cells indicated that the evolved viruses were more effective against 4T1 cells than the parental virus or a reference oncolytic VSV (MΔ51), but showed no increased efficacy against CT26 cells. In vivo assays using 4T1 syngeneic tumor models showed that one of the evolved lines significantly delayed tumor growth compared to mice treated with the parental virus or untreated controls, and was able to induce transient tumor suppression. Our results show that RNA viruses can be specifically adapted typical cancer features such as p53 inactivation, and illustrate the usefulness of experimental evolution for oncolytic virotherapy.
format	article
author	Raquel Garijo Pablo Hernández-Alonso Carmen Rivas Jean-Simon Diallo Rafael Sanjuán
author_facet	Raquel Garijo Pablo Hernández-Alonso Carmen Rivas Jean-Simon Diallo Rafael Sanjuán
author_sort	Raquel Garijo
title	Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells.
title_short	Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells.
title_full	Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells.
title_fullStr	Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells.
title_full_unstemmed	Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells.
title_sort	experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/c084da314e344d8193753f27dfe89078
work_keys_str_mv	AT raquelgarijo experimentalevolutionofanoncolyticvesicularstomatitisviruswithincreasedselectivityforp53deficientcells AT pablohernandezalonso experimentalevolutionofanoncolyticvesicularstomatitisviruswithincreasedselectivityforp53deficientcells AT carmenrivas experimentalevolutionofanoncolyticvesicularstomatitisviruswithincreasedselectivityforp53deficientcells AT jeansimondiallo experimentalevolutionofanoncolyticvesicularstomatitisviruswithincreasedselectivityforp53deficientcells AT rafaelsanjuan experimentalevolutionofanoncolyticvesicularstomatitisviruswithincreasedselectivityforp53deficientcells
_version_	1718414127887548416

Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells.

Ejemplares similares