Activity of core modified 10-23 DNAzymes against HCV

Autores
Robaldo, Laura; Berzal Herranz, Alfredo; Montserrat, Javier Marcelo; Iribarren, Adolfo Marcelo
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The highly conserved untranslated regions of the hepatitis C virus (HCV) play a fundamental role in viral translation and replication and are therefore attractive targets for drug development. A set of modified DNAzymes carrying (2′R)-, (2′S)-2′-deoxy-2′-C-methyl- and -2′-O-methylnucleosides at various positions of the catalytic core were assayed against the 5′-internal ribosome entry site element (5′-IRES) region of HCV. Intracellular stability studies showed that the highest stabilization effects were obtained when the DNAzymes′ cores were jointly modified with 2′-C-methyl- and 2′-O-methylnucleosides, yielding an increase by up to fivefold in the total DNAzyme accumulation within the cell milieu within 48 h of transfection. Different regions of the HCV IRES were explored with unmodified 10–23 DNAzymes for accessibility. A subset of these positions was tested for DNAzyme activity using an HCV IRES-firefly luciferase translation-dependent RNA (IRES-FLuc) transcript, in the rabbit reticulocyte lysate system and in the Huh-7 human hepatocarcinoma cell line. Inhibition of IRES-dependent translation by up to 65 % was observed for DNAzymes targeting its 285 position, and it was also shown that the modified DNAzymes are as active as the unmodified one.
Fil: Robaldo, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
Fil: Berzal Herranz, Alfredo. Instituto de Parasitología y Biomedicina “López-Neyra”; España
Fil: Montserrat, Javier Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad Nacional de General Sarmiento. Instituto de Ciencias; Argentina
Fil: Iribarren, Adolfo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química. Laboratorio de Biotransformaciones; Argentina
Materia
Viruses (Hcv)
10-23 Dnazyme
2?-C-Methylnucleosides
2?-O-Methyl Nucleosides
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/3963
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/3963
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Activity of core modified 10-23 DNAzymes against HCVRobaldo, LauraBerzal Herranz, AlfredoMontserrat, Javier MarceloIribarren, Adolfo MarceloViruses (Hcv)10-23 Dnazyme2?-C-Methylnucleosides2?-O-Methyl Nucleosideshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The highly conserved untranslated regions of the hepatitis C virus (HCV) play a fundamental role in viral translation and replication and are therefore attractive targets for drug development. A set of modified DNAzymes carrying (2′R)-, (2′S)-2′-deoxy-2′-C-methyl- and -2′-O-methylnucleosides at various positions of the catalytic core were assayed against the 5′-internal ribosome entry site element (5′-IRES) region of HCV. Intracellular stability studies showed that the highest stabilization effects were obtained when the DNAzymes′ cores were jointly modified with 2′-C-methyl- and 2′-O-methylnucleosides, yielding an increase by up to fivefold in the total DNAzyme accumulation within the cell milieu within 48 h of transfection. Different regions of the HCV IRES were explored with unmodified 10–23 DNAzymes for accessibility. A subset of these positions was tested for DNAzyme activity using an HCV IRES-firefly luciferase translation-dependent RNA (IRES-FLuc) transcript, in the rabbit reticulocyte lysate system and in the Huh-7 human hepatocarcinoma cell line. Inhibition of IRES-dependent translation by up to 65 % was observed for DNAzymes targeting its 285 position, and it was also shown that the modified DNAzymes are as active as the unmodified one.Fil: Robaldo, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Berzal Herranz, Alfredo. Instituto de Parasitología y Biomedicina “López-Neyra”; EspañaFil: Montserrat, Javier Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad Nacional de General Sarmiento. Instituto de Ciencias; ArgentinaFil: Iribarren, Adolfo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química. Laboratorio de Biotransformaciones; ArgentinaWiley2014-07-30info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/3963Robaldo, Laura; Berzal Herranz, Alfredo; Montserrat, Javier Marcelo; Iribarren, Adolfo Marcelo; Activity of core modified 10-23 DNAzymes against HCV; Wiley; Chemmedchem; 9; 9; 30-7-2014; 2172–21771860-7179enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/cmdc.201402222/abstractinfo:eu-repo/semantics/altIdentifier/doi/DOI:10.1002/cmdc.201402222info:eu-repo/semantics/altIdentifier/issn/1860-7179info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:55Zoai:ri.conicet.gov.ar:11336/3963instacron: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:34982025-09-03 09:58:55.844CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activity of core modified 10-23 DNAzymes against HCV
title Activity of core modified 10-23 DNAzymes against HCV
spellingShingle Activity of core modified 10-23 DNAzymes against HCV
Robaldo, Laura
Viruses (Hcv)
10-23 Dnazyme
2?-C-Methylnucleosides
2?-O-Methyl Nucleosides
title_short Activity of core modified 10-23 DNAzymes against HCV
title_full Activity of core modified 10-23 DNAzymes against HCV
title_fullStr Activity of core modified 10-23 DNAzymes against HCV
title_full_unstemmed Activity of core modified 10-23 DNAzymes against HCV
title_sort Activity of core modified 10-23 DNAzymes against HCV
dc.creator.none.fl_str_mv Robaldo, Laura
Berzal Herranz, Alfredo
Montserrat, Javier Marcelo
Iribarren, Adolfo Marcelo
author Robaldo, Laura
author_facet Robaldo, Laura
Berzal Herranz, Alfredo
Montserrat, Javier Marcelo
Iribarren, Adolfo Marcelo
author_role author
author2 Berzal Herranz, Alfredo
Montserrat, Javier Marcelo
Iribarren, Adolfo Marcelo
author2_role author
author
author
dc.subject.none.fl_str_mv Viruses (Hcv)
10-23 Dnazyme
2?-C-Methylnucleosides
2?-O-Methyl Nucleosides
topic Viruses (Hcv)
10-23 Dnazyme
2?-C-Methylnucleosides
2?-O-Methyl Nucleosides
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The highly conserved untranslated regions of the hepatitis C virus (HCV) play a fundamental role in viral translation and replication and are therefore attractive targets for drug development. A set of modified DNAzymes carrying (2′R)-, (2′S)-2′-deoxy-2′-C-methyl- and -2′-O-methylnucleosides at various positions of the catalytic core were assayed against the 5′-internal ribosome entry site element (5′-IRES) region of HCV. Intracellular stability studies showed that the highest stabilization effects were obtained when the DNAzymes′ cores were jointly modified with 2′-C-methyl- and 2′-O-methylnucleosides, yielding an increase by up to fivefold in the total DNAzyme accumulation within the cell milieu within 48 h of transfection. Different regions of the HCV IRES were explored with unmodified 10–23 DNAzymes for accessibility. A subset of these positions was tested for DNAzyme activity using an HCV IRES-firefly luciferase translation-dependent RNA (IRES-FLuc) transcript, in the rabbit reticulocyte lysate system and in the Huh-7 human hepatocarcinoma cell line. Inhibition of IRES-dependent translation by up to 65 % was observed for DNAzymes targeting its 285 position, and it was also shown that the modified DNAzymes are as active as the unmodified one.
Fil: Robaldo, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
Fil: Berzal Herranz, Alfredo. Instituto de Parasitología y Biomedicina “López-Neyra”; España
Fil: Montserrat, Javier Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad Nacional de General Sarmiento. Instituto de Ciencias; Argentina
Fil: Iribarren, Adolfo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química. Laboratorio de Biotransformaciones; Argentina
description The highly conserved untranslated regions of the hepatitis C virus (HCV) play a fundamental role in viral translation and replication and are therefore attractive targets for drug development. A set of modified DNAzymes carrying (2′R)-, (2′S)-2′-deoxy-2′-C-methyl- and -2′-O-methylnucleosides at various positions of the catalytic core were assayed against the 5′-internal ribosome entry site element (5′-IRES) region of HCV. Intracellular stability studies showed that the highest stabilization effects were obtained when the DNAzymes′ cores were jointly modified with 2′-C-methyl- and 2′-O-methylnucleosides, yielding an increase by up to fivefold in the total DNAzyme accumulation within the cell milieu within 48 h of transfection. Different regions of the HCV IRES were explored with unmodified 10–23 DNAzymes for accessibility. A subset of these positions was tested for DNAzyme activity using an HCV IRES-firefly luciferase translation-dependent RNA (IRES-FLuc) transcript, in the rabbit reticulocyte lysate system and in the Huh-7 human hepatocarcinoma cell line. Inhibition of IRES-dependent translation by up to 65 % was observed for DNAzymes targeting its 285 position, and it was also shown that the modified DNAzymes are as active as the unmodified one.
publishDate 2014
dc.date.none.fl_str_mv 2014-07-30
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/11336/3963
Robaldo, Laura; Berzal Herranz, Alfredo; Montserrat, Javier Marcelo; Iribarren, Adolfo Marcelo; Activity of core modified 10-23 DNAzymes against HCV; Wiley; Chemmedchem; 9; 9; 30-7-2014; 2172–2177
1860-7179
url http://hdl.handle.net/11336/3963
identifier_str_mv Robaldo, Laura; Berzal Herranz, Alfredo; Montserrat, Javier Marcelo; Iribarren, Adolfo Marcelo; Activity of core modified 10-23 DNAzymes against HCV; Wiley; Chemmedchem; 9; 9; 30-7-2014; 2172–2177
1860-7179
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/cmdc.201402222/abstract
info:eu-repo/semantics/altIdentifier/doi/DOI:10.1002/cmdc.201402222
info:eu-repo/semantics/altIdentifier/issn/1860-7179
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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 13.13397

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