Convection-enhanced delivery of AAV2-PrPshRNA in prion-infected mice.
Prion disease is caused by a single pathogenic protein (PrPSc), an abnormal conformer of the normal cellular prion protein PrPC. Depletion of PrPC in prion knockout mice makes them resistant to prion disease. Thus, gene silencing of the Prnp gene is a promising effective therapeutic approach. Here,...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4035323?pdf=render |
| _version_ | 1818327473119559680 |
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| author | Misol Ahn Krystyna Bajsarowicz Abby Oehler Azucena Lemus Krystof Bankiewicz Stephen J DeArmond |
| author_facet | Misol Ahn Krystyna Bajsarowicz Abby Oehler Azucena Lemus Krystof Bankiewicz Stephen J DeArmond |
| author_sort | Misol Ahn |
| collection | DOAJ |
| description | Prion disease is caused by a single pathogenic protein (PrPSc), an abnormal conformer of the normal cellular prion protein PrPC. Depletion of PrPC in prion knockout mice makes them resistant to prion disease. Thus, gene silencing of the Prnp gene is a promising effective therapeutic approach. Here, we examined adeno-associated virus vector type 2 encoding a short hairpin RNA targeting Prnp mRNA (AAV2-PrP-shRNA) to suppress PrPC expression both in vitro and in vivo. AAV2-PrP-shRNA treatment suppressed PrP levels and prevented dendritic degeneration in RML-infected brain aggregate cultures. Infusion of AAV2-PrP-shRNA-eGFP into the thalamus of CD-1 mice showed that eGFP was transported to the cerebral cortex via anterograde transport and the overall PrPC levels were reduced by ∼ 70% within 4 weeks. For therapeutic purposes, we treated RML-infected CD-1 mice with AAV2-PrP-shRNA beginning at 50 days post inoculation. Although AAV2-PrP-shRNA focally suppressed PrPSc formation in the thalamic infusion site by ∼ 75%, it did not suppress PrPSc formation efficiently in other regions of the brain. Survival of mice was not extended compared to the untreated controls. Global suppression of PrPC in the brain is required for successful therapy of prion diseases. |
| first_indexed | 2024-12-13T12:16:49Z |
| format | Article |
| id | doaj.art-66afdabe53f04fc4be59002124875636 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T12:16:49Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-66afdabe53f04fc4be590021248756362022-12-21T23:46:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9849610.1371/journal.pone.0098496Convection-enhanced delivery of AAV2-PrPshRNA in prion-infected mice.Misol AhnKrystyna BajsarowiczAbby OehlerAzucena LemusKrystof BankiewiczStephen J DeArmondPrion disease is caused by a single pathogenic protein (PrPSc), an abnormal conformer of the normal cellular prion protein PrPC. Depletion of PrPC in prion knockout mice makes them resistant to prion disease. Thus, gene silencing of the Prnp gene is a promising effective therapeutic approach. Here, we examined adeno-associated virus vector type 2 encoding a short hairpin RNA targeting Prnp mRNA (AAV2-PrP-shRNA) to suppress PrPC expression both in vitro and in vivo. AAV2-PrP-shRNA treatment suppressed PrP levels and prevented dendritic degeneration in RML-infected brain aggregate cultures. Infusion of AAV2-PrP-shRNA-eGFP into the thalamus of CD-1 mice showed that eGFP was transported to the cerebral cortex via anterograde transport and the overall PrPC levels were reduced by ∼ 70% within 4 weeks. For therapeutic purposes, we treated RML-infected CD-1 mice with AAV2-PrP-shRNA beginning at 50 days post inoculation. Although AAV2-PrP-shRNA focally suppressed PrPSc formation in the thalamic infusion site by ∼ 75%, it did not suppress PrPSc formation efficiently in other regions of the brain. Survival of mice was not extended compared to the untreated controls. Global suppression of PrPC in the brain is required for successful therapy of prion diseases.http://europepmc.org/articles/PMC4035323?pdf=render |
| spellingShingle | Misol Ahn Krystyna Bajsarowicz Abby Oehler Azucena Lemus Krystof Bankiewicz Stephen J DeArmond Convection-enhanced delivery of AAV2-PrPshRNA in prion-infected mice. PLoS ONE |
| title | Convection-enhanced delivery of AAV2-PrPshRNA in prion-infected mice. |
| title_full | Convection-enhanced delivery of AAV2-PrPshRNA in prion-infected mice. |
| title_fullStr | Convection-enhanced delivery of AAV2-PrPshRNA in prion-infected mice. |
| title_full_unstemmed | Convection-enhanced delivery of AAV2-PrPshRNA in prion-infected mice. |
| title_short | Convection-enhanced delivery of AAV2-PrPshRNA in prion-infected mice. |
| title_sort | convection enhanced delivery of aav2 prpshrna in prion infected mice |
| url | http://europepmc.org/articles/PMC4035323?pdf=render |
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