Lentivector-mediated RNAi efficiently suppresses prion protein and prolongs survival of scrapie-infected mice

Speaker: 高家民                                                                    Date: 2007.03.14

Commentator: 王憲威 老師                                                 Time: 13:00~14:00

Abstract:

        Prion diseases, such as Creutzfeldt-Jakob disease and scrapie, are fatal and neurodegenerative, and there are no any effective treatments available.  Present studies showed that PrP^sc, a self-replicating, infectious, and protease-resistant protein homologous to cellular protein PrP^c, is the only essential component in prion diseases.  Since the reducing of PrP^c expression is suggested to be an effective way to control the prion disease.  Therefore, in the study, the authors generated a lentiviral vector which encodes short hairpin RNA (shRNA) to against prion protein gene (prnp).  Lentivector (LVsh512) which expresses short hairpin RNAs against PrP^c, are found to suppress not only PrPc expression in neuroblastoma or primary neuronal cells but also prion replication in persistent-infected murine neuroblastoma cell line.  In in vivo study, they also found that LVsh512 significantly reduced PrP^c expression in the brain of PrP^c overexpressing mice.  Finally, the authors created a chimeric mouse which expresses LVsh512 and found that the level of PrP^c in the brains of these mice was reduced.  After scrapie inoculation, the mean survival time of LVsh512 expressing mice was significantly longer than that of control mice.  Therefore, this study demonstrated that shRNA specific to PrP^c has therapeutic potential in control of prion disease.