Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice
Mice deficient for the cellular prion protein (PrPC) do not develop prion disease; accordingly, gene-based strategies to diminish PrPC expression are of interest. We synthesized a series of chemically modified antisense oligonucleotides (ASOs) targeted against mouse Prnp messenger RNA (mRNA) and ide...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2012-01-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253116300671 |
| _version_ | 1811256053402173440 |
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| author | Karah Nazor Friberg Gene Hung Ed Wancewicz Kurt Giles Chris Black Sue Freier Frank Bennett Stephen J DeArmond Yevgeniy Freyman Pierre Lessard Sina Ghaemmaghami Stanley B Prusiner |
| author_facet | Karah Nazor Friberg Gene Hung Ed Wancewicz Kurt Giles Chris Black Sue Freier Frank Bennett Stephen J DeArmond Yevgeniy Freyman Pierre Lessard Sina Ghaemmaghami Stanley B Prusiner |
| author_sort | Karah Nazor Friberg |
| collection | DOAJ |
| description | Mice deficient for the cellular prion protein (PrPC) do not develop prion disease; accordingly, gene-based strategies to diminish PrPC 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 PrPC 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 (PrPSc). 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. |
| first_indexed | 2024-04-12T17:34:19Z |
| format | Article |
| id | doaj.art-e903ab1e0ba844ac9d3324d05a35cd78 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-12T17:34:19Z |
| publishDate | 2012-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-e903ab1e0ba844ac9d3324d05a35cd782022-12-22T03:23:02ZengElsevierMolecular Therapy: Nucleic Acids2162-25312012-01-011C10.1038/mtna.2011.6Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected MiceKarah Nazor Friberg0Gene Hung1Ed Wancewicz2Kurt Giles3Chris Black4Sue Freier5Frank Bennett6Stephen J DeArmond7Yevgeniy Freyman8Pierre Lessard9Sina Ghaemmaghami10Stanley B Prusiner11Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, USAIsis Pharmaceuticals, Inc., San Francisco, California, USAIsis Pharmaceuticals, Inc., San Francisco, California, USAInstitute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, USAIsis Pharmaceuticals, Inc., San Francisco, California, USAIsis Pharmaceuticals, Inc., San Francisco, California, USAIsis Pharmaceuticals, Inc., San Francisco, California, USAInstitute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, USAInstitute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, USAInstitute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, USAInstitute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, USAInstitute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, USAMice deficient for the cellular prion protein (PrPC) do not develop prion disease; accordingly, gene-based strategies to diminish PrPC 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 PrPC 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 (PrPSc). 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.http://www.sciencedirect.com/science/article/pii/S2162253116300671 |
| spellingShingle | Karah Nazor Friberg Gene Hung Ed Wancewicz Kurt Giles Chris Black Sue Freier Frank Bennett Stephen J DeArmond Yevgeniy Freyman Pierre Lessard Sina Ghaemmaghami Stanley B Prusiner Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice Molecular Therapy: Nucleic Acids |
| 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 |
| url | http://www.sciencedirect.com/science/article/pii/S2162253116300671 |
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