Convection-enhanced delivery of AAV2-PrPshRNA in prion-infected mice
| Autor: | Krystyna Bajsarowicz, Azucena Lemus, Misol Ahn, Abby Oehler, Krystof S. Bankiewicz, Stephen J. DeArmond |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Prions
viruses animal diseases Central nervous system Genetic Vectors lcsh:Medicine Biology Prion Proteins Viral vector PRNP Prion Diseases Small hairpin RNA Gene Knockout Techniques Mice Thalamus In vivo Zoonoses mental disorders medicine Medicine and Health Sciences Gene silencing Animals PrPC Proteins RNA Small Interfering lcsh:Science Molecular Biology Techniques Molecular Biology Clinical Genetics Messenger RNA Multidisciplinary lcsh:R Biology and Life Sciences Genetic Therapy Gene Therapy Dependovirus Virology 3. Good health Cell biology nervous system diseases medicine.anatomical_structure Infectious Diseases Veterinary Diseases Knockout mouse lcsh:Q Female Veterinary Science Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 5, p e98496 (2014) Bankiewicz, Krzysztof; Ahn, M; Bajsarowicz, K; Oehler, A; Lemus, A; & DeArmond, SJ. (2014). Convection-enhanced delivery of AAV2-PrPshRNA in prion-infected mice.. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/6tz843jn |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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