Immune responses, not promoter inactivation, are responsible for decreased long-term expression following plasmid gene transfer into skeletal muscle

• Published in: FEBS letters Vol. 407; no. 2; pp. 164 - 168
• Main Authors: Wells, K.E, Maule, J, Kingston, R, Foster, K, McMahon, J, Damien, E, Poole, A, Wells, D.J
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 28.04.1997
• Subjects: AIDS/HIV; Animals; beta-Galactosidase - genetics; beta-Galactosidase - immunology; Chloramphenicol O-Acetyltransferase - genetics; Chloramphenicol O-Acetyltransferase - immunology; Cytotoxic T-cells; Cytotoxicity, Immunologic; Gene Expression; Gene therapy; Gene Transfer Techniques; Genetic Therapy - methods; Immunoglobulin Isotypes - blood; Immunology; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Muscle Fibers, Skeletal - pathology; Muscle, Skeletal - immunology; Muscle, Skeletal - pathology; Plasmid DNA; Recombinant Proteins - immunology; Skeletal muscle; Th1 Cells - immunology; Immunology; Gene therapy; Plasmid DNA; Cytotoxic T-cells; Skeletal muscle
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(97)00329-3

Long-term high-level in vivo gene expression appears to depend on the promoter chosen to drive the gene of choice. In many cases the promoter appears to `switch off' some time after in vivo gene transfer. We demonstrate that, following intramuscular injection of β-galactosidase reporter plasmids, promoter `switch off' is due to elimination of fibres expressing the transferred reporter gene by activation of a Th1 (cytotoxic) immune response. This finding, in the absence of stimulation of the immune system by viral vector proteins, has implications not only for gene transfer experiments but for the future of muscle-directed gene therapy.