Details

Autor(en) / Beteiligte

• Pflanz, Heike
• Vana, Karen
• Mitteregger, Gerda
• Pace, Claudia
• Messow, Diana
• Sedlaczek, Cilli
• Nikles, Daphne
• Kretzschmar, Hans A
• Weiss, Stefan F. T

Titel

Microinjection of lentiviral vectors expressing small interfering RNAs directed against laminin receptor precursor mRNA prolongs the pre-clinical phase in scrapie-infected mice

Ist Teil von

• Journal of general virology, 2009-01, Vol.90 (1), p.269-274

Ort / Verlag

Reading: Soc General Microbiol

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• 1 Laboratorium für Molekulare Biologie - Genzentrum - Institut für Biochemie der LMU München, Feodor-Lynen Str. 25, D-81377 München, Germany 2 Zentrum für Neuropathologie und Prionforschung der LMU München, Feodor-Lynen-Str. 23, D-81377 München, Germany Correspondence Stefan Weiss weiss{at}lmb.uni-muenchen.de 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 PrP Sc 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 PrP Sc levels by 36 and 41 %, respectively, concomitant with a significant prolongation of the pre-clinical phase. Lentiviral vectors expressing siRNAs targeting LRP mRNA represent a novel delivery system for the treatment of transmissible spongiform encephalopathies. These authors contributed equally to this work. A figure showing the siRNA target sequences within the murine LRP mRNA is available with the online version of this paper.