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Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice

Mice deficient for the cellular prion protein (PrP(C)) do not develop prion disease; accordingly, gene-based strategies to diminish PrP(C) expression are of interest. We synthesized a series of chemically modified antisense oligonucleotides (ASOs) targeted against mouse Prnp messenger RNA (mRNA) and...

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Autores principales: Nazor Friberg, Karah, Hung, Gene, Wancewicz, Ed, Giles, Kurt, Black, Chris, Freier, Sue, Bennett, Frank, DeArmond, Stephen J, Freyman, Yevgeniy, Lessard, Pierre, Ghaemmaghami, Sina, Prusiner, Stanley B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381600/
https://www.ncbi.nlm.nih.gov/pubmed/23344724
http://dx.doi.org/10.1038/mtna.2011.6
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author Nazor Friberg, Karah
Hung, Gene
Wancewicz, Ed
Giles, Kurt
Black, Chris
Freier, Sue
Bennett, Frank
DeArmond, Stephen J
Freyman, Yevgeniy
Lessard, Pierre
Ghaemmaghami, Sina
Prusiner, Stanley B
author_facet Nazor Friberg, Karah
Hung, Gene
Wancewicz, Ed
Giles, Kurt
Black, Chris
Freier, Sue
Bennett, Frank
DeArmond, Stephen J
Freyman, Yevgeniy
Lessard, Pierre
Ghaemmaghami, Sina
Prusiner, Stanley B
author_sort Nazor Friberg, Karah
collection PubMed
description Mice deficient for the cellular prion protein (PrP(C)) do not develop prion disease; accordingly, gene-based strategies to diminish PrP(C) expression are of interest. We synthesized a series of chemically modified antisense oligonucleotides (ASOs) targeted against mouse Prnp messenger RNA (mRNA) and identified those that were most effective in decreasing PrP(C) expression. Those ASOs were also evaluated in scrapie-infected cultured cells (ScN2a) for their efficacy in diminishing the levels of the disease-causing prion protein (PrP(Sc)). When the optimal ASO was infused intracerebrally into FVB mice over a 14-day period beginning 1 day after infection with the Rocky Mountain Laboratory (RML) strain of mouse prions, a prolongation of the incubation period of almost 2 months was observed. Whether ASOs can be used to develop an effective therapy for patients dying of Creutzfeldt–Jakob disease remains to be established.
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spelling pubmed-33816002012-07-03 Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice Nazor Friberg, Karah Hung, Gene Wancewicz, Ed Giles, Kurt Black, Chris Freier, Sue Bennett, Frank DeArmond, Stephen J Freyman, Yevgeniy Lessard, Pierre Ghaemmaghami, Sina Prusiner, Stanley B Mol Ther Nucleic Acids Original Article Mice deficient for the cellular prion protein (PrP(C)) do not develop prion disease; accordingly, gene-based strategies to diminish PrP(C) expression are of interest. We synthesized a series of chemically modified antisense oligonucleotides (ASOs) targeted against mouse Prnp messenger RNA (mRNA) and identified those that were most effective in decreasing PrP(C) expression. Those ASOs were also evaluated in scrapie-infected cultured cells (ScN2a) for their efficacy in diminishing the levels of the disease-causing prion protein (PrP(Sc)). When the optimal ASO was infused intracerebrally into FVB mice over a 14-day period beginning 1 day after infection with the Rocky Mountain Laboratory (RML) strain of mouse prions, a prolongation of the incubation period of almost 2 months was observed. Whether ASOs can be used to develop an effective therapy for patients dying of Creutzfeldt–Jakob disease remains to be established. Nature Publishing Group 2012-02 2012-02-07 /pmc/articles/PMC3381600/ /pubmed/23344724 http://dx.doi.org/10.1038/mtna.2011.6 Text en Copyright © 2012 American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-nd/3.0/ Molecular Therapy-Nucleic Acids is an open-access journal published by Nature Publishing Group. This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Nazor Friberg, Karah
Hung, Gene
Wancewicz, Ed
Giles, Kurt
Black, Chris
Freier, Sue
Bennett, Frank
DeArmond, Stephen J
Freyman, Yevgeniy
Lessard, Pierre
Ghaemmaghami, Sina
Prusiner, Stanley B
Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice
title Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice
title_full Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice
title_fullStr Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice
title_full_unstemmed Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice
title_short Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice
title_sort intracerebral infusion of antisense oligonucleotides into prion-infected mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381600/
https://www.ncbi.nlm.nih.gov/pubmed/23344724
http://dx.doi.org/10.1038/mtna.2011.6
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