Journal
JOURNAL OF GENERAL VIROLOGY
Volume 90, Issue -, Pages 269-274Publisher
MICROBIOLOGY SOC
DOI: 10.1099/vir.0.004168-0
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Funding
- Bavarian Government [AZ: 55.2-1-54-44/05]
- Bundesministerium fur Bildung und Forschung [01-KO-0514]
- European Commission [NoE NeuroPrion FOOD-CT 2004-506579]
- Deutsche Forschungsgemeinschaft [WE 2664/2-1]
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We examined therapeutic in vitro and in vivo approaches using lentivirus-based packaging of small interfering RNAs (siRNAs) targeting the non-integrin laminin receptor mRNA for treatment and prevention of prion disorders. Transfection of N2aSc(+) cells with recombinant plasmids expressing three different siRNAs, significantly reduced both the LRP (laminin receptor precursor) and PrPSc levels by approximately 40-60%. Stereotactic intracerebral microinjection of recombinant lentiviral vectors LVsiRNA-LRP 7 and 9 into the cortex of C57BL/6 wild-type mice resulted in a significant reduction of the LR levels in the cortex 15 days post-injection by 62 and 82%, respectively. Intracerebral RML inoculation of C57BL/6 mice after microinjection with recombinant lentiviral vector LVsiRNA-LRP 7 into the hippocampus resulted in a significant reduction of both LRP and PrPSc levels by 36 and 41%, respectively, concomitant with a significant prolongation of the pre-clinical phase. Lentiviral vectors expressing siRNAs targeting LIRP mRNA represent a novel delivery system for the treatment of transmissible spongiform encephalopathies.
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