Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence

Autores
Bravo, Soraya; Núñez Aguilera, Felipe Javier; Cruzat, Fernando; Cafferata, Eduardo Gustavo Alfredo; De Ferrari, Giancarlo V; Montecino, Martín; Podhajcer, Osvaldo Luis
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cancer development involves changes driven by the epigenetic machinery, including nucleosome positioning. Recently, the concept that adenoviral replication may be driven by tumor specific promoters (TSPs) gained support, and several conditionally replicative adenoviruses (CRAd) exhibited therapeutic efficacy in clinical trials. Here, we show for the first time that placing a nucleosome positioning sequence (NPS) upstream of a TSP combined with Wnt-responsive motifs (pART enhancer) enhanced the TSP transcriptional activity and increased the lytic activity of a CRAd. pART enhanced the transcriptional activity of the gastrointestinal cancer (GIC)-specific REG1A promoter (REG1A-pr); moreover, pART also increased the in vitro lytic activity of a CRAd whose replication was driven by REG1A-Pr. The pART enhancer effect in vitro and in vivo was strictly dependent on the presence of the NPS. Indeed, deletion of the NPS was strongly deleterious for the in vivo antitumor efficacy of the CRAd on orthotopically established pancreatic xenografts. pART also enhanced the specific activity ofmother heterologous promoters; moreover, the NPS was also able to enhance the responsiveness of hypoxia- and NFκ B-response elements. We conclude that NPS could be useful for gene therapy approaches in cancer as wellas other diseases.
Fil: Bravo, Soraya. Universidad Andrés Bello; Chile
Fil: Núñez Aguilera, Felipe Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Cruzat, Fernando. Universidad de Concepción; Chile
Fil: Cafferata, Eduardo Gustavo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: De Ferrari, Giancarlo V. Universidad Andrés Bello; Chile
Fil: Montecino, Martín. Universidad Andrés Bello; Chile
Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Materia
VIROTERAPIA
CANCER
NUCLEOSOMA
MOTIVOS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/102803
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/102803
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning SequenceBravo, SorayaNúñez Aguilera, Felipe JavierCruzat, FernandoCafferata, Eduardo Gustavo AlfredoDe Ferrari, Giancarlo VMontecino, MartínPodhajcer, Osvaldo LuisVIROTERAPIACANCERNUCLEOSOMAMOTIVOShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cancer development involves changes driven by the epigenetic machinery, including nucleosome positioning. Recently, the concept that adenoviral replication may be driven by tumor specific promoters (TSPs) gained support, and several conditionally replicative adenoviruses (CRAd) exhibited therapeutic efficacy in clinical trials. Here, we show for the first time that placing a nucleosome positioning sequence (NPS) upstream of a TSP combined with Wnt-responsive motifs (pART enhancer) enhanced the TSP transcriptional activity and increased the lytic activity of a CRAd. pART enhanced the transcriptional activity of the gastrointestinal cancer (GIC)-specific REG1A promoter (REG1A-pr); moreover, pART also increased the in vitro lytic activity of a CRAd whose replication was driven by REG1A-Pr. The pART enhancer effect in vitro and in vivo was strictly dependent on the presence of the NPS. Indeed, deletion of the NPS was strongly deleterious for the in vivo antitumor efficacy of the CRAd on orthotopically established pancreatic xenografts. pART also enhanced the specific activity ofmother heterologous promoters; moreover, the NPS was also able to enhance the responsiveness of hypoxia- and NFκ B-response elements. We conclude that NPS could be useful for gene therapy approaches in cancer as wellas other diseases.Fil: Bravo, Soraya. Universidad Andrés Bello; ChileFil: Núñez Aguilera, Felipe Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Cruzat, Fernando. Universidad de Concepción; ChileFil: Cafferata, Eduardo Gustavo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: De Ferrari, Giancarlo V. Universidad Andrés Bello; ChileFil: Montecino, Martín. Universidad Andrés Bello; ChileFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaNature Publishing Group2013-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/102803Bravo, Soraya; Núñez Aguilera, Felipe Javier; Cruzat, Fernando; Cafferata, Eduardo Gustavo Alfredo; De Ferrari, Giancarlo V; et al.; Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence; Nature Publishing Group; Molecular Therapy (print); 21; 7; 4-2013; 1403-14121525-0016CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://linkinghub.elsevier.com/retrieve/pii/S1525001616319645info:eu-repo/semantics/altIdentifier/doi/10.1038/mt.2013.93info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:06:13Zoai:ri.conicet.gov.ar:11336/102803instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:06:13.742CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence
title Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence
spellingShingle Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence
Bravo, Soraya
VIROTERAPIA
CANCER
NUCLEOSOMA
MOTIVOS
title_short Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence
title_full Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence
title_fullStr Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence
title_full_unstemmed Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence
title_sort Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence
dc.creator.none.fl_str_mv Bravo, Soraya
Núñez Aguilera, Felipe Javier
Cruzat, Fernando
Cafferata, Eduardo Gustavo Alfredo
De Ferrari, Giancarlo V
Montecino, Martín
Podhajcer, Osvaldo Luis
author Bravo, Soraya
author_facet Bravo, Soraya
Núñez Aguilera, Felipe Javier
Cruzat, Fernando
Cafferata, Eduardo Gustavo Alfredo
De Ferrari, Giancarlo V
Montecino, Martín
Podhajcer, Osvaldo Luis
author_role author
author2 Núñez Aguilera, Felipe Javier
Cruzat, Fernando
Cafferata, Eduardo Gustavo Alfredo
De Ferrari, Giancarlo V
Montecino, Martín
Podhajcer, Osvaldo Luis
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv VIROTERAPIA
CANCER
NUCLEOSOMA
MOTIVOS
topic VIROTERAPIA
CANCER
NUCLEOSOMA
MOTIVOS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cancer development involves changes driven by the epigenetic machinery, including nucleosome positioning. Recently, the concept that adenoviral replication may be driven by tumor specific promoters (TSPs) gained support, and several conditionally replicative adenoviruses (CRAd) exhibited therapeutic efficacy in clinical trials. Here, we show for the first time that placing a nucleosome positioning sequence (NPS) upstream of a TSP combined with Wnt-responsive motifs (pART enhancer) enhanced the TSP transcriptional activity and increased the lytic activity of a CRAd. pART enhanced the transcriptional activity of the gastrointestinal cancer (GIC)-specific REG1A promoter (REG1A-pr); moreover, pART also increased the in vitro lytic activity of a CRAd whose replication was driven by REG1A-Pr. The pART enhancer effect in vitro and in vivo was strictly dependent on the presence of the NPS. Indeed, deletion of the NPS was strongly deleterious for the in vivo antitumor efficacy of the CRAd on orthotopically established pancreatic xenografts. pART also enhanced the specific activity ofmother heterologous promoters; moreover, the NPS was also able to enhance the responsiveness of hypoxia- and NFκ B-response elements. We conclude that NPS could be useful for gene therapy approaches in cancer as wellas other diseases.
Fil: Bravo, Soraya. Universidad Andrés Bello; Chile
Fil: Núñez Aguilera, Felipe Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Cruzat, Fernando. Universidad de Concepción; Chile
Fil: Cafferata, Eduardo Gustavo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: De Ferrari, Giancarlo V. Universidad Andrés Bello; Chile
Fil: Montecino, Martín. Universidad Andrés Bello; Chile
Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
description Cancer development involves changes driven by the epigenetic machinery, including nucleosome positioning. Recently, the concept that adenoviral replication may be driven by tumor specific promoters (TSPs) gained support, and several conditionally replicative adenoviruses (CRAd) exhibited therapeutic efficacy in clinical trials. Here, we show for the first time that placing a nucleosome positioning sequence (NPS) upstream of a TSP combined with Wnt-responsive motifs (pART enhancer) enhanced the TSP transcriptional activity and increased the lytic activity of a CRAd. pART enhanced the transcriptional activity of the gastrointestinal cancer (GIC)-specific REG1A promoter (REG1A-pr); moreover, pART also increased the in vitro lytic activity of a CRAd whose replication was driven by REG1A-Pr. The pART enhancer effect in vitro and in vivo was strictly dependent on the presence of the NPS. Indeed, deletion of the NPS was strongly deleterious for the in vivo antitumor efficacy of the CRAd on orthotopically established pancreatic xenografts. pART also enhanced the specific activity ofmother heterologous promoters; moreover, the NPS was also able to enhance the responsiveness of hypoxia- and NFκ B-response elements. We conclude that NPS could be useful for gene therapy approaches in cancer as wellas other diseases.
publishDate 2013
dc.date.none.fl_str_mv 2013-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/102803
Bravo, Soraya; Núñez Aguilera, Felipe Javier; Cruzat, Fernando; Cafferata, Eduardo Gustavo Alfredo; De Ferrari, Giancarlo V; et al.; Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence; Nature Publishing Group; Molecular Therapy (print); 21; 7; 4-2013; 1403-1412
1525-0016
CONICET Digital
CONICET
url http://hdl.handle.net/11336/102803
identifier_str_mv Bravo, Soraya; Núñez Aguilera, Felipe Javier; Cruzat, Fernando; Cafferata, Eduardo Gustavo Alfredo; De Ferrari, Giancarlo V; et al.; Enhanced CRAd Activity Using Enhancer Motifs Driven by a Nucleosome Positioning Sequence; Nature Publishing Group; Molecular Therapy (print); 21; 7; 4-2013; 1403-1412
1525-0016
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://linkinghub.elsevier.com/retrieve/pii/S1525001616319645
info:eu-repo/semantics/altIdentifier/doi/10.1038/mt.2013.93
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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