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dc.contributor.authorTerrazas, Montserrat
dc.contributor.authorIvani, Ivan
dc.contributor.authorVillegas, Núria
dc.contributor.authorParis, Clément
dc.contributor.authorSalvans, Cándida
dc.contributor.authorBrun-Heath, Isabelle
dc.contributor.authorOrozco, Modesto
dc.contributor.otherBarcelona Supercomputing Center
dc.date.accessioned2016-06-17T14:51:26Z
dc.date.available2016-06-17T14:51:26Z
dc.date.issued2016-05-19
dc.identifier.citationTerrazas, Montserrat [et al.]. Rational design of novel N-alkyl-N capped biostable RNA nanostructures for efficient long-term inhibition of gene expression. "Nucleic Acids Research", 19 Maig 2016, vol. 44, núm. 9, p. 4354-4367.
dc.identifier.issn0305-1048
dc.identifier.urihttp://hdl.handle.net/2117/88139
dc.description.abstractComputational techniques have been used to design a novel class of RNA architecture with expected improved resistance to nuclease degradation, while showing interference RNA activity. The in silico designed structure consists of a 24–29 bp duplex RNA region linked on both ends by N-alkyl-N dimeric nucleotides (BCn dimers; n = number of carbon atoms of the alkyl chain). A series of N-alkyl-N capped dumbbell-shaped structures were efficiently synthesized by double ligation of BCn-loop hairpins. The resulting BCn-loop dumbbells displayed experimentally higher biostability than their 3′-N-alkyl-N linear version, and were active against a range of mRNA targets. We studied first the effect of the alkyl chain and stem lengths on RNAi activity in a screen involving two series of dumbbell analogues targeting Renilla and Firefly luciferase genes. The best dumbbell design (containing BC6 loops and 29 bp) was successfully used to silence GRB7 expression in HER2+ breast cancer cells for longer periods of time than natural siRNAs and known biostable dumbbells. This BC6-loop dumbbell-shaped structure displayed greater anti-proliferative activity than natural siRNAs.
dc.description.sponsorshipInstituto de Salud Carlos III [Miguel Servet Program, CP13/00211, 205024141 to M.T.]; Spanish MINECO [BIO2012–32869 and BIO2015-64802-R toM.O.]; AGAUR (toM.O.); ERCCouncil (SimDNA, grant 291433, to M.O.). M.O. is an ICREA Academia fellow. Funding for open access charge: ERC Council [grant 291433 (simDNA)].
dc.format.extent14 p.
dc.language.isoeng
dc.publisherOxford University Press (OUP)
dc.rightsAttribution-NonCommercial-NoDerivs 4.0 Spain
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/es/
dc.subjectÀrees temàtiques de la UPC::Enginyeria biomèdica
dc.subject.lcshRNA
dc.subject.lcshMolecular dynamics
dc.subject.lcshDNA--Analysis
dc.subject.otherRNA
dc.subject.otherBreast cancer cells
dc.subject.otherRNA interference (RNAi)
dc.subject.otherOligonucleotide sequences
dc.titleRational design of novel N-alkyl-N capped biostable RNA nanostructures for efficient long-term inhibition of gene expression
dc.typeArticle
dc.subject.lemacADN
dc.subject.lemacDinàmica molecular
dc.identifier.doi10.1093/nar/gkw169
dc.description.peerreviewedPeer Reviewed
dc.relation.publisherversionhttp://nar.oxfordjournals.org/content/44/9/4354.long
dc.rights.accessOpen Access
dc.description.versionPostprint (published version)
dc.relation.projectidinfo:eu-repo/grantAgreement/MINECO/1PE/BIO2012-32869
dc.relation.projectidinfo:eu-repo/grantAgreement/MINECO//BIO2015-64802-R/ES/ESTUDIO DE FORMAS INUSUALES Y TENSIONADAS DE LOS ACIDOS NUCLEICOS DE INTERES BIOMEDICO Y BIOTECNOLOGICO./
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/FP7/291433/EU/Advanced multiscale simulation of DNA/SIMDNA
local.citation.publicationNameNucleic Acids Research
local.citation.volume44
local.citation.number9
local.citation.startingPage4354
local.citation.endingPage4367
dc.identifier.pmid26975656


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