Semliki Forest virus vectors expressing transforming growth factor beta inhibit experimental autoimmune encephalomyelitis in Balb/c mice
| Autor: | Tiina I. Kuusinen, Markus Vähä-Koskela, Jari E. Heikkilä, Petra T. Furu, Jeanette C. Holmlund-Hampf, Ari Hinkkanen |
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| Rok vydání: | 2007 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental Genetic enhancement Genetic Vectors Biophysics Gene delivery Semliki Forest virus Biochemistry Virus BALB/c Viral vector Transforming Growth Factor beta1 Mice medicine Animals RNA Messenger Molecular Biology Brain Chemistry Mice Inbred BALB C biology Experimental autoimmune encephalomyelitis Brain Genetic Therapy Cell Biology Transforming growth factor beta biology.organism_classification medicine.disease Semliki forest virus Virology Protein Biosynthesis Immunology biology.protein Female Immunotherapy |
| Zdroj: | Biochemical and Biophysical Research Communications. 355:776-781 |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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