title: Myosin regulatory elements as vectors for gene transfer by intramuscular injection.
abstract: Intramuscular injection of plasmid constructs promises to be an effective way of carrying out gene therapy for muscle disorders as well as using muscle as an in vivo expression system for disorders that involve the gene product being secreted into the bloodstream. The effectiveness of this method depends on the design of the cassette used for the expression of the cDNA of the introduced gene. We tested the levels of expression achieved by a number of muscle-specific promoters and a myosin light chain enhancer when spliced to the reporter gene chloramphenicol acetyltransferase (CAT), in vitro and in vivo by injection into fast and slow muscles of the mouse. The results show that the highest levels of expression are achieved by a combination of a truncated myosin heavy chain promoter and the enhancer, and that a whole range of expression levels is obtained with the other combinations tested. The data show that a cassette based on these elements should provide efficient vectors for the introduction and expression of genes following intramuscular injection of naked DNA.
authors.affiliation: Department of Anatomy and Developmental Biology, Royal Free Hospital School of Medicine, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Skarli
authors.forename: A
authors.initials: A
authors.lastname: Kiri
authors.forename: G
authors.initials: G
authors.lastname: Vrbova
authors.forename: C A
authors.initials: CA
authors.lastname: Lee
authors.forename: G
authors.initials: G
authors.lastname: Goldspink
mesh_terms: D000818:Animals; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D051379:Mice; D008810:Mice, Inbred C57BL; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism; D018994:Myosin Light Chains / Q000235:genetics*; D010957:Plasmids; D015202:Protein Engineering
chemical_list: D018994:Myosin Light Chains