Microinjection of lentiviral vectors expressing small interfering RNAs directed against laminin receptor precursor mRNA prolongs the pre-clinical phase in scrapie-infected mice.
J Gen Virol
; 90(Pt 1): 269-74, 2009 Jan.
Article
in En
| MEDLINE
| ID: mdl-19088298
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Scrapie
/
RNA, Messenger
/
Receptors, Laminin
/
Lentivirus
/
RNA, Small Interfering
/
Genetic Vectors
Limits:
Animals
Language:
En
Journal:
J Gen Virol
Year:
2009
Document type:
Article
Affiliation country:
Germany