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 charact...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2007-04, Vol.355 (3), p.776-781
Main Authors: Vähä-Koskela, Markus J.V., Kuusinen, Tiina I., Holmlund-Hampf, Jeanette C., Furu, Petra T., Heikkilä, Jari E., Hinkkanen, Ari E.
Format: Article
Language:English
Subjects:
Animals
Brain - metabolism
Brain Chemistry
Central nervous system (CNS)
Encephalomyelitis, Autoimmune, Experimental - therapy
Experimental autoimmune encephalomyelitis (EAE)
Female
Gene therapy
Genetic Therapy
Genetic Vectors - genetics
Immunotherapy
Mice
Mice, Inbred BALB C
Protein Biosynthesis
RNA, Messenger - analysis
RNA, Messenger - metabolism
Semliki Forest virus
Semliki Forest virus (SFV)
Semliki forest virus - genetics
Transforming growth factor beta 1 (TGF-β1)
Transforming Growth Factor beta1 - genetics
Transforming Growth Factor beta1 - metabolism
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Summary: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-β1). Biological activity of the expressed inserts was demonstrated by PAI-1 promoter driven luciferase production in mink cells and TGF-β1 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2007.02.026