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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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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. |
format | Online Article Text |
id | pubmed-3381600 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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