IMMUNE-RESPONSES, NOT PROMOTER INACTIVATION, ARE RESPONSIBLE FOR DECREASED LONG-TERM EXPRESSION FOLLOWING PLASMID GENE-TRANSFER INTO SKELETAL-MUSCLE

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 promote r appears to 'switch off' some time after in vivo gene transfer, We de monstrate that, following intramuscular injection of beta-galactosidas e reporter plasmids, promoter 'switch off is due to elimination of fib res expressing the transferred reporter gene by activation of a Th1 (c ytotoxic) immune response, This finding, in the absence of stimulation of the immune system by viral vector proteins, has implications not o nly for gene transfer experiments but for the future of muscle-directe d gene therapy. (C) 1997 Federation of European Biochemical Societies.