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dc.contributor.author
Giménez, Carla Alejandra  
dc.contributor.author
Ielpi, Marcelo  
dc.contributor.author
Mutto, Adrián Angel  
dc.contributor.author
Grosembacher, Luis  
dc.contributor.author
Argibay, Pablo  
dc.contributor.author
Pereyra Bonnet, Federico Alberto  
dc.date.available
2018-05-03T19:30:07Z  
dc.date.issued
2016-04  
dc.identifier.citation
Giménez, Carla Alejandra; Ielpi, Marcelo; Mutto, Adrián Angel; Grosembacher, Luis; Argibay, Pablo; et al.; CRISPR-on system for the activation of the endogenous human INS gene; Nature Publishing Group; Gene Therapy; 23; 4-2016; 543–547  
dc.identifier.issn
0969-7128  
dc.identifier.uri
http://hdl.handle.net/11336/44026  
dc.description.abstract
Advances in the field of epigenetics have allowed the design of new therapeutic strategies to address complex diseases such as type 1 diabetes (T1D). Clustered regularly interspaced short palindromic repeats (CRISPR)-on is a novel and powerful RNA-guided transcriptional activator system that can turn on specific gene expression; however, it remains unclear whether this system can be widely used or whether its use will be restricted depending on cell types, methylation promoter statuses or the capacity to modulate chromatin state. Our results revealed that the CRISPR-on system fused with transcriptional activators (dCas9-VP160) activated endogenous human INS, which is a silenced gene with a fully methylated promoter. Similarly, we observed a synergistic effect on gene activation when multiple single guide RNAs were used, and the transcriptional activation was maintained until day 21. Regarding the epigenetic profile, the targeted promoter gene did not exhibit alteration in its methylation status but rather exhibited altered levels of H3K9ac following treatment. Importantly, we showed that dCas9-VP160 acts on patients' cells in vitro, particularly the fibroblasts of patients with T1D.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Nature Publishing Group  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Crisprs  
dc.subject
Rna  
dc.subject
Esc  
dc.subject
Insulin  
dc.subject.classification
Otras Ciencias Biológicas  
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Ciencias Biológicas  
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CIENCIAS NATURALES Y EXACTAS  
dc.title
CRISPR-on system for the activation of the endogenous human INS gene  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2018-05-03T13:59:27Z  
dc.journal.volume
23  
dc.journal.pagination
543–547  
dc.journal.pais
Reino Unido  
dc.journal.ciudad
Londres  
dc.description.fil
Fil: Giménez, Carla Alejandra. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Ielpi, Marcelo. Hospital Italiano; Argentina  
dc.description.fil
Fil: Mutto, Adrián Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina  
dc.description.fil
Fil: Grosembacher, Luis. Hospital Italiano; Argentina  
dc.description.fil
Fil: Argibay, Pablo. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Pereyra Bonnet, Federico Alberto. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.journal.title
Gene Therapy  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/gt.2016.28  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/gt201628