Increased in vivo inhibition of gene expression by combining RNA interference and U1 inhibition

Inhibition of gene expression can be achieved with RNA interference (RNAi) or U1 small nuclear RNA-snRNA-interference (U1i). U1i is based on U1 inhibitors (U1in), U1 snRNA molecules modified to inhibit polyadenylation of a target pre-mRNA. In culture, we have shown that the combination of RNAi and U...

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Autores: Blazquez, L. (Lorea)|||/items/2cffcc24-94df-4926-a53e-2a8952b533c3, Gonzalez-Rojas, S.J. (Sandra Jovanna)|||/items/249612d6-4e27-4e2b-a403-75821de7b7cb, Abad-Cacho, A. (Amaya)|||/items/a84b92ad-d23d-4679-90b1-78cf672cb74f, Razquin, N. (Nerea)|||/items/b59c7d85-e337-4aa0-bf68-ad9aaa54009d, Abad, X. (Xabier)|||/items/050ca3bc-2ff5-40d8-a24c-72cb58605954, Fortes, P. (Puri)|||/items/4b719a39-983d-402a-bb2a-2bdd276be18e
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/23173
Acceso en línea:https://hdl.handle.net/10171/23173
Access Level:acceso abierto
Palabra clave:RNA Interference
RNA, Small Nuclear/antagonists & inhibitors
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spelling Increased in vivo inhibition of gene expression by combining RNA interference and U1 inhibitionBlazquez, L. (Lorea)|||/items/2cffcc24-94df-4926-a53e-2a8952b533c3Gonzalez-Rojas, S.J. (Sandra Jovanna)|||/items/249612d6-4e27-4e2b-a403-75821de7b7cbAbad-Cacho, A. (Amaya)|||/items/a84b92ad-d23d-4679-90b1-78cf672cb74fRazquin, N. (Nerea)|||/items/b59c7d85-e337-4aa0-bf68-ad9aaa54009dAbad, X. (Xabier)|||/items/050ca3bc-2ff5-40d8-a24c-72cb58605954Fortes, P. (Puri)|||/items/4b719a39-983d-402a-bb2a-2bdd276be18eRNA InterferenceRNA, Small Nuclear/antagonists & inhibitorsInhibition of gene expression can be achieved with RNA interference (RNAi) or U1 small nuclear RNA-snRNA-interference (U1i). U1i is based on U1 inhibitors (U1in), U1 snRNA molecules modified to inhibit polyadenylation of a target pre-mRNA. In culture, we have shown that the combination of RNAi and U1i results in stronger inhibition of reporter or endogenous genes than that obtained using either of the techniques alone. We have now used these techniques to inhibit gene expression in mice. We show that U1ins can induce strong inhibition of the expression of target genes in vivo. Furthermore, combining U1i and RNAi results in synergistic inhibitions also in mice. This is shown for the inhibition of hepatitis B virus (HBV) sequences or endogenous Notch1. Surprisingly, inhibition obtained by combining a U1in and a RNAi mediator is higher than that obtained by combining two U1ins or two RNAi mediators. Our results suggest that RNAi and U1i cooperate by unknown mechanisms to result in synergistic inhibitions. Analysis of toxicity and specificity indicates that expression of U1i inhibitors is safe. Therefore, we believe that the combination of RNAi and U1i will be a good option to block damaging endogenous genes, HBV and other infectious agents in vivo.Oxford University PressDadun. Depósito Académico Digital Universidad de Navarra20122012-09-2420122012-01-0120122012-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/23173reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/231732026-06-21T12:47:57Z
dc.title.none.fl_str_mv Increased in vivo inhibition of gene expression by combining RNA interference and U1 inhibition
title Increased in vivo inhibition of gene expression by combining RNA interference and U1 inhibition
spellingShingle Increased in vivo inhibition of gene expression by combining RNA interference and U1 inhibition
Blazquez, L. (Lorea)|||/items/2cffcc24-94df-4926-a53e-2a8952b533c3
RNA Interference
RNA, Small Nuclear/antagonists & inhibitors
title_short Increased in vivo inhibition of gene expression by combining RNA interference and U1 inhibition
title_full Increased in vivo inhibition of gene expression by combining RNA interference and U1 inhibition
title_fullStr Increased in vivo inhibition of gene expression by combining RNA interference and U1 inhibition
title_full_unstemmed Increased in vivo inhibition of gene expression by combining RNA interference and U1 inhibition
title_sort Increased in vivo inhibition of gene expression by combining RNA interference and U1 inhibition
dc.creator.none.fl_str_mv Blazquez, L. (Lorea)|||/items/2cffcc24-94df-4926-a53e-2a8952b533c3
Gonzalez-Rojas, S.J. (Sandra Jovanna)|||/items/249612d6-4e27-4e2b-a403-75821de7b7cb
Abad-Cacho, A. (Amaya)|||/items/a84b92ad-d23d-4679-90b1-78cf672cb74f
Razquin, N. (Nerea)|||/items/b59c7d85-e337-4aa0-bf68-ad9aaa54009d
Abad, X. (Xabier)|||/items/050ca3bc-2ff5-40d8-a24c-72cb58605954
Fortes, P. (Puri)|||/items/4b719a39-983d-402a-bb2a-2bdd276be18e
author Blazquez, L. (Lorea)|||/items/2cffcc24-94df-4926-a53e-2a8952b533c3
author_facet Blazquez, L. (Lorea)|||/items/2cffcc24-94df-4926-a53e-2a8952b533c3
Gonzalez-Rojas, S.J. (Sandra Jovanna)|||/items/249612d6-4e27-4e2b-a403-75821de7b7cb
Abad-Cacho, A. (Amaya)|||/items/a84b92ad-d23d-4679-90b1-78cf672cb74f
Razquin, N. (Nerea)|||/items/b59c7d85-e337-4aa0-bf68-ad9aaa54009d
Abad, X. (Xabier)|||/items/050ca3bc-2ff5-40d8-a24c-72cb58605954
Fortes, P. (Puri)|||/items/4b719a39-983d-402a-bb2a-2bdd276be18e
author_role author
author2 Gonzalez-Rojas, S.J. (Sandra Jovanna)|||/items/249612d6-4e27-4e2b-a403-75821de7b7cb
Abad-Cacho, A. (Amaya)|||/items/a84b92ad-d23d-4679-90b1-78cf672cb74f
Razquin, N. (Nerea)|||/items/b59c7d85-e337-4aa0-bf68-ad9aaa54009d
Abad, X. (Xabier)|||/items/050ca3bc-2ff5-40d8-a24c-72cb58605954
Fortes, P. (Puri)|||/items/4b719a39-983d-402a-bb2a-2bdd276be18e
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv RNA Interference
RNA, Small Nuclear/antagonists & inhibitors
topic RNA Interference
RNA, Small Nuclear/antagonists & inhibitors
description Inhibition of gene expression can be achieved with RNA interference (RNAi) or U1 small nuclear RNA-snRNA-interference (U1i). U1i is based on U1 inhibitors (U1in), U1 snRNA molecules modified to inhibit polyadenylation of a target pre-mRNA. In culture, we have shown that the combination of RNAi and U1i results in stronger inhibition of reporter or endogenous genes than that obtained using either of the techniques alone. We have now used these techniques to inhibit gene expression in mice. We show that U1ins can induce strong inhibition of the expression of target genes in vivo. Furthermore, combining U1i and RNAi results in synergistic inhibitions also in mice. This is shown for the inhibition of hepatitis B virus (HBV) sequences or endogenous Notch1. Surprisingly, inhibition obtained by combining a U1in and a RNAi mediator is higher than that obtained by combining two U1ins or two RNAi mediators. Our results suggest that RNAi and U1i cooperate by unknown mechanisms to result in synergistic inhibitions. Analysis of toxicity and specificity indicates that expression of U1i inhibitors is safe. Therefore, we believe that the combination of RNAi and U1i will be a good option to block damaging endogenous genes, HBV and other infectious agents in vivo.
publishDate 2012
dc.date.none.fl_str_mv 2012
2012-09-24
2012
2012-01-01
2012
2012-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/23173
url https://hdl.handle.net/10171/23173
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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