Generation of recombinant adenovirus expressing siRNA against the L mRNA of measles virus and subacute sclerosing panencephalitis virus.
Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by prolonged persistent infection of the central nervous system with a measles virus (MV) mutant called SSPE virus. At present, there is no effective treatment to completely cure SSPE and development of a new therapeutic measure(s) against this fatal slow virus infection is needed. We previously reported that replication of MV and SSPE virus was effectively inhibited by small interfering RNA (siRNA), either chemically synthetic or plasmid-driven ones, that were targeted against different sequences of the mRNA for the L protein of MV. In this study, we have generated recombinant adenovirus expressing the siRNAs (rAd-siRNA-MV-L2, -L4 and -L5) and demonstrated that these rAd-siRNAs efficiently inhibited replication of MV and SSPE virus in a dose-dependent manner. Due to their high capacity for gene delivery to nerve cells and the potential to inhibit SSPE virus replication, the rAd-siRNAs could be a good candidate for a novel therapeutic measure against SSPE.
Otaki
Momoko
M
Division of Microbiology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan.
Jiang
Da-Peng
DP
Sasayama
Mikiko
M
Nagano-Fujii
Motoko
M
Hotta
Hak
H
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D002522:Chlorocebus aethiops; D006801:Humans; D008459:Measles virus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011995:Recombination, Genetic; D013190:SSPE Virus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013344:Subacute Sclerosing Panencephalitis / Q000821:virology; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014764:Viral Proteins