siRNA and RNAi optimization

The discovery and examination of the posttranscriptional gene regulatory mechanism known as RNA interference (RNAi) contributed to the identification of small interfering RNA (siRNA) and the comprehension of its enormous potential for clinical purposes. Theoretically, the ability of specific target...

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Detalles Bibliográficos
Autores: Alagia, Adele, Eritja Casadellà, Ramón
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/131031
Acceso en línea:http://hdl.handle.net/10261/131031
Access Level:acceso abierto
Palabra clave:RNAi
siRNA
miRNA
RISC
Ago2
Off-target effects
Chemical modification
structural modification
Exosomes
delivery
RNA microsponges
HDL-like particles
dumbbell
si-siRNA
aiRNA
asiRNA
is-siRNA
dsi-RNA
ss-siRNA
id ES_f37fe8df6fcbe60ef868b808672a5fe2
oai_identifier_str oai:digital.csic.es:10261/131031
network_acronym_str ES
network_name_str España
repository_id_str
spelling siRNA and RNAi optimizationAlagia, AdeleEritja Casadellà, RamónRNAisiRNAmiRNARISCAgo2Off-target effectsChemical modificationstructural modificationExosomesdeliveryRNA microspongesHDL-like particlesdumbbellsi-siRNAaiRNAasiRNAis-siRNAdsi-RNAss-siRNAThe discovery and examination of the posttranscriptional gene regulatory mechanism known as RNA interference (RNAi) contributed to the identification of small interfering RNA (siRNA) and the comprehension of its enormous potential for clinical purposes. Theoretically, the ability of specific target gene downregulation makes the RNAi pathway an appealing solution for several diseases. Despite numerous hurdles resulting from the inherent properties of siRNA molecule and proper delivery to the target tissue, more than 50 RNA-based drugs are currently under clinical testing. In this work, we analyze the recent literature in the optimization of siRNA molecules. In detail, we focused on describing the most recent advances of siRNA field aimed at optimize siRNA pharmacokinetic properties. Special attention has been given in describing the impact of RNA modifications in the potential off-target effects (OTEs) such as saturation of the RNAi machinery, passenger strand-mediated silencing, immunostimulation, and miRNA-like OTEs as well as to recent developments on the delivery issue. The novel delivery systems and modified siRNA provide significant steps toward the development of reliable siRNA molecules for therapeutic use. © 2016 Wiley Periodicals, Inc.The work is supported by grants of the European Commission (NMP4-LA-2011-262943, MULTIFUN), the Spanish Ministry of Economy (CTQ2014-52588-R, RTC-2014-2038-1), Generalitat de Catalunya (2014/SGR/624) and the Instituto de Salud Carlos III (CB06_01_0019) with assistance from the European Regional Development Fund.Peer reviewedJohn Wiley & SonsMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201620162016info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/131031reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2014-52588-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/RTC-2014-2038-1info:eu-repo/grantAgreement/EC/FP7/262943http://dx.doi.org/10.1021/10.1002/wrna.1337Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1310312026-05-22T06:33:51Z
dc.title.none.fl_str_mv siRNA and RNAi optimization
title siRNA and RNAi optimization
spellingShingle siRNA and RNAi optimization
Alagia, Adele
RNAi
siRNA
miRNA
RISC
Ago2
Off-target effects
Chemical modification
structural modification
Exosomes
delivery
RNA microsponges
HDL-like particles
dumbbell
si-siRNA
aiRNA
asiRNA
is-siRNA
dsi-RNA
ss-siRNA
title_short siRNA and RNAi optimization
title_full siRNA and RNAi optimization
title_fullStr siRNA and RNAi optimization
title_full_unstemmed siRNA and RNAi optimization
title_sort siRNA and RNAi optimization
dc.creator.none.fl_str_mv Alagia, Adele
Eritja Casadellà, Ramón
author Alagia, Adele
author_facet Alagia, Adele
Eritja Casadellà, Ramón
author_role author
author2 Eritja Casadellà, Ramón
author2_role author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv RNAi
siRNA
miRNA
RISC
Ago2
Off-target effects
Chemical modification
structural modification
Exosomes
delivery
RNA microsponges
HDL-like particles
dumbbell
si-siRNA
aiRNA
asiRNA
is-siRNA
dsi-RNA
ss-siRNA
topic RNAi
siRNA
miRNA
RISC
Ago2
Off-target effects
Chemical modification
structural modification
Exosomes
delivery
RNA microsponges
HDL-like particles
dumbbell
si-siRNA
aiRNA
asiRNA
is-siRNA
dsi-RNA
ss-siRNA
description The discovery and examination of the posttranscriptional gene regulatory mechanism known as RNA interference (RNAi) contributed to the identification of small interfering RNA (siRNA) and the comprehension of its enormous potential for clinical purposes. Theoretically, the ability of specific target gene downregulation makes the RNAi pathway an appealing solution for several diseases. Despite numerous hurdles resulting from the inherent properties of siRNA molecule and proper delivery to the target tissue, more than 50 RNA-based drugs are currently under clinical testing. In this work, we analyze the recent literature in the optimization of siRNA molecules. In detail, we focused on describing the most recent advances of siRNA field aimed at optimize siRNA pharmacokinetic properties. Special attention has been given in describing the impact of RNA modifications in the potential off-target effects (OTEs) such as saturation of the RNAi machinery, passenger strand-mediated silencing, immunostimulation, and miRNA-like OTEs as well as to recent developments on the delivery issue. The novel delivery systems and modified siRNA provide significant steps toward the development of reliable siRNA molecules for therapeutic use. © 2016 Wiley Periodicals, Inc.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/131031
url http://hdl.handle.net/10261/131031
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2014-52588-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/RTC-2014-2038-1
info:eu-repo/grantAgreement/EC/FP7/262943
http://dx.doi.org/10.1021/10.1002/wrna.1337
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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