siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides

Autores
Dellafiore, María Andrea; Aviñó, Anna; Alagia, Adele; Montserrat, Javier Marcelo; Iribarren, Adolfo Marcelo; Eritja, Ramon
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
(2′S)-2′-Deoxy-2′-C-methyluridine and (2′R)-2′-deoxy-2′-C-meth-yluridine were incorporated in the 3’-overhang region of the sense and antisense strands and in positions 2 and 5 of the seed region of siRNA duplexes directed against Renilla luciferase, whereas (2′S)-2′-deoxy-2′-C-methylcytidine was incorporated in the 6-position of the seed region of the same constructions. A dual luciferase reporter assay in transfected HeLa cells was used as a model system to measure the IC50 values of 24 different modified duplexes. The best results were obtained by the substitution of one thymidine unit in the antisense 3’-overhang region by (2′S)-or (2′R)-2′-deoxy-2′-C-methyluridine, reducing IC50 to half of the value observed for the natural control. The selectivity of the modified siRNA was measured, it being found that modifications in positions 5 and 6 of the seed region had a positive effect on the ON/OFF activity.
Fil: Dellafiore, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Aviñó, Anna. Consejo Superior de Investigaciones Científicas. Instituto de Química Avanzada de Catalunya; España. Ciber Bioingenieria, Biomateriales y Nanomedicina; España
Fil: Alagia, Adele. Consejo Superior de Investigaciones Científicas. Instituto de Química Avanzada de Catalunya; España. Ciber Bioingenieria, Biomateriales y Nanomedicina; España
Fil: Montserrat, Javier Marcelo. Universidad Nacional de General Sarmiento. Instituto de Ciencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Iribarren, Adolfo Marcelo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Eritja, Ramon. Consejo Superior de Investigaciones Científicas. Instituto de Química Avanzada de Catalunya; España. Ciber Bioingenieria, Biomateriales y Nanomedicina; España
Materia
ACTIVITY RELATIONSHIPS
DEOXYMETHYLPYRIMIDINE BASES
NUCLEOSIDES
SIRNA
STABILITY
STRUCTURE
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:11336/98721
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/98721
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosidesDellafiore, María AndreaAviñó, AnnaAlagia, AdeleMontserrat, Javier MarceloIribarren, Adolfo MarceloEritja, RamonACTIVITY RELATIONSHIPSDEOXYMETHYLPYRIMIDINE BASESNUCLEOSIDESSIRNASTABILITYSTRUCTUREhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1(2′S)-2′-Deoxy-2′-C-methyluridine and (2′R)-2′-deoxy-2′-C-meth-yluridine were incorporated in the 3’-overhang region of the sense and antisense strands and in positions 2 and 5 of the seed region of siRNA duplexes directed against Renilla luciferase, whereas (2′S)-2′-deoxy-2′-C-methylcytidine was incorporated in the 6-position of the seed region of the same constructions. A dual luciferase reporter assay in transfected HeLa cells was used as a model system to measure the IC50 values of 24 different modified duplexes. The best results were obtained by the substitution of one thymidine unit in the antisense 3’-overhang region by (2′S)-or (2′R)-2′-deoxy-2′-C-methyluridine, reducing IC50 to half of the value observed for the natural control. The selectivity of the modified siRNA was measured, it being found that modifications in positions 5 and 6 of the seed region had a positive effect on the ON/OFF activity.Fil: Dellafiore, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Aviñó, Anna. Consejo Superior de Investigaciones Científicas. Instituto de Química Avanzada de Catalunya; España. Ciber Bioingenieria, Biomateriales y Nanomedicina; EspañaFil: Alagia, Adele. Consejo Superior de Investigaciones Científicas. Instituto de Química Avanzada de Catalunya; España. Ciber Bioingenieria, Biomateriales y Nanomedicina; EspañaFil: Montserrat, Javier Marcelo. Universidad Nacional de General Sarmiento. Instituto de Ciencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Iribarren, Adolfo Marcelo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Eritja, Ramon. Consejo Superior de Investigaciones Científicas. Instituto de Química Avanzada de Catalunya; España. Ciber Bioingenieria, Biomateriales y Nanomedicina; EspañaWiley VCH Verlag2018-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/mswordapplication/pdfhttp://hdl.handle.net/11336/98721Dellafiore, María Andrea; Aviñó, Anna; Alagia, Adele; Montserrat, Javier Marcelo; Iribarren, Adolfo Marcelo; et al.; siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides; Wiley VCH Verlag; Chembiochem; 19; 13; 3-2018; 1409-14131439-4227CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/cbic.201800077info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/pdf/10.1002/cbic.201800077info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:33:11Zoai:ri.conicet.gov.ar:11336/98721instacron: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:34982025-09-29 09:33:12.177CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides
title siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides
spellingShingle siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides
Dellafiore, María Andrea
ACTIVITY RELATIONSHIPS
DEOXYMETHYLPYRIMIDINE BASES
NUCLEOSIDES
SIRNA
STABILITY
STRUCTURE
title_short siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides
title_full siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides
title_fullStr siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides
title_full_unstemmed siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides
title_sort siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides
dc.creator.none.fl_str_mv Dellafiore, María Andrea
Aviñó, Anna
Alagia, Adele
Montserrat, Javier Marcelo
Iribarren, Adolfo Marcelo
Eritja, Ramon
author Dellafiore, María Andrea
author_facet Dellafiore, María Andrea
Aviñó, Anna
Alagia, Adele
Montserrat, Javier Marcelo
Iribarren, Adolfo Marcelo
Eritja, Ramon
author_role author
author2 Aviñó, Anna
Alagia, Adele
Montserrat, Javier Marcelo
Iribarren, Adolfo Marcelo
Eritja, Ramon
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ACTIVITY RELATIONSHIPS
DEOXYMETHYLPYRIMIDINE BASES
NUCLEOSIDES
SIRNA
STABILITY
STRUCTURE
topic ACTIVITY RELATIONSHIPS
DEOXYMETHYLPYRIMIDINE BASES
NUCLEOSIDES
SIRNA
STABILITY
STRUCTURE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv (2′S)-2′-Deoxy-2′-C-methyluridine and (2′R)-2′-deoxy-2′-C-meth-yluridine were incorporated in the 3’-overhang region of the sense and antisense strands and in positions 2 and 5 of the seed region of siRNA duplexes directed against Renilla luciferase, whereas (2′S)-2′-deoxy-2′-C-methylcytidine was incorporated in the 6-position of the seed region of the same constructions. A dual luciferase reporter assay in transfected HeLa cells was used as a model system to measure the IC50 values of 24 different modified duplexes. The best results were obtained by the substitution of one thymidine unit in the antisense 3’-overhang region by (2′S)-or (2′R)-2′-deoxy-2′-C-methyluridine, reducing IC50 to half of the value observed for the natural control. The selectivity of the modified siRNA was measured, it being found that modifications in positions 5 and 6 of the seed region had a positive effect on the ON/OFF activity.
Fil: Dellafiore, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Aviñó, Anna. Consejo Superior de Investigaciones Científicas. Instituto de Química Avanzada de Catalunya; España. Ciber Bioingenieria, Biomateriales y Nanomedicina; España
Fil: Alagia, Adele. Consejo Superior de Investigaciones Científicas. Instituto de Química Avanzada de Catalunya; España. Ciber Bioingenieria, Biomateriales y Nanomedicina; España
Fil: Montserrat, Javier Marcelo. Universidad Nacional de General Sarmiento. Instituto de Ciencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Iribarren, Adolfo Marcelo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Eritja, Ramon. Consejo Superior de Investigaciones Científicas. Instituto de Química Avanzada de Catalunya; España. Ciber Bioingenieria, Biomateriales y Nanomedicina; España
description (2′S)-2′-Deoxy-2′-C-methyluridine and (2′R)-2′-deoxy-2′-C-meth-yluridine were incorporated in the 3’-overhang region of the sense and antisense strands and in positions 2 and 5 of the seed region of siRNA duplexes directed against Renilla luciferase, whereas (2′S)-2′-deoxy-2′-C-methylcytidine was incorporated in the 6-position of the seed region of the same constructions. A dual luciferase reporter assay in transfected HeLa cells was used as a model system to measure the IC50 values of 24 different modified duplexes. The best results were obtained by the substitution of one thymidine unit in the antisense 3’-overhang region by (2′S)-or (2′R)-2′-deoxy-2′-C-methyluridine, reducing IC50 to half of the value observed for the natural control. The selectivity of the modified siRNA was measured, it being found that modifications in positions 5 and 6 of the seed region had a positive effect on the ON/OFF activity.
publishDate 2018
dc.date.none.fl_str_mv 2018-03
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/11336/98721
Dellafiore, María Andrea; Aviñó, Anna; Alagia, Adele; Montserrat, Javier Marcelo; Iribarren, Adolfo Marcelo; et al.; siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides; Wiley VCH Verlag; Chembiochem; 19; 13; 3-2018; 1409-1413
1439-4227
CONICET Digital
CONICET
url http://hdl.handle.net/11336/98721
identifier_str_mv Dellafiore, María Andrea; Aviñó, Anna; Alagia, Adele; Montserrat, Javier Marcelo; Iribarren, Adolfo Marcelo; et al.; siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides; Wiley VCH Verlag; Chembiochem; 19; 13; 3-2018; 1409-1413
1439-4227
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/cbic.201800077
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/pdf/10.1002/cbic.201800077
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/msword
application/pdf
dc.publisher.none.fl_str_mv Wiley VCH Verlag
publisher.none.fl_str_mv Wiley VCH Verlag
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
_version_ 1844613018485260288
score 13.070432

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