Semliki Forest virus vectors expressing transforming growth factor beta inhibit experimental autoimmune encephalomyelitis in Balb/c mice.
Cytokine immunomodulation of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, has remained a formidable treatment option, but access into the CNS is hampered due to the impermeability of the blood-brain barrier. In this report, we describe the construction and characterization of CNS-homing gene delivery/therapy vectors based on avirulent Semliki Forest virus (SFV) expressing either native or mutant transforming growth factor beta 1 (TGF-beta1). Biological activity of the expressed inserts was demonstrated by PAI-1 promoter driven luciferase production in mink cells and TGF-beta1 mRNA was demonstrated in the CNS of virus treated mice by in situ hybridization and RT-PCR. Both vectors, when given intraperitoneally to EAE mice significantly reduced disease severity compared to untreated mice. Our results imply that immunomodulation by neurotropic viral vectors may offer a promising treatment strategy for autoimmune CNS disorders.
Vähä-Koskela
Markus J V
MJ
Department of Biochemistry and Pharmacy, Abo Akademi University, Tykistökatu 6A, FI-20520 Turku, Finland. makoskel@abo.fi
Kuusinen
Tiina I
TI
Holmlund-Hampf
Jeanette C
JC
Furu
Petra T
PT
Heikkilä
Jari E
JE
Hinkkanen
Ari E
AE
D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012672:Semliki forest virus / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1