Method for enhancing myoblast migration and invasion in the context of gene therapy

Abstract

A novel, empirically derived composition of cytokines and myoblasts is described, that allows for the migration of myoblasts through connective barriers, along with methods employing the composition in the in vivo migration of myoblasts for therapeutic purposes and gene therapy, as well as methods for the identification of agents that are agonistic or antagonistic to myoblast migration in vitro or in vivo.

1 . A composition, comprising myoblasts transfected with a gene encoding a metalloprotease.  
     
     
         2 . The composition of    claim 1   , wherein said myoblasts have been co-transfected with a gene encoding a therapeutic gene product.  
     
     
         3 . The composition of    claim 2   , wherein said therapeutic gene product is dystrophin.  
     
     
         4 . A composition, comprising a host, said host comprising myoblasts transfected with a gene encoding a metalloprotease.  
     
     
         5 . The composition of    claim 4   , wherein said myoblasts have been co-transfected with a gene encoding a therapeutic gene product.  
     
     
         6 . The composition of    claim 5   , wherein said therapeutic gene product is dystrophin.  
     
     
         7 . A method, comprising: 
 a) providing i) transfected myoblasts, said transfected myoblasts transfected with a gene encoding a therapeutic gene product, ii) a host, and iii) fibroblast growth factor and fibronectin;    b) culturing said transfected myoblasts in the presence of said fibroblast growth factor and said fibronectin to create cultured, transfected myoblasts; and    c) introducing said cultured, transfected myoblasts into said host.    
     
     
         8 . The method of    claim 7   , wherein said myoblasts have been co-transfected with a gene encoding a metalloprotease.  
     
     
         9 . The method of    claim 7   , wherein said transfected myoblasts were provided by the host.  
     
     
         10 . The method of    claim 7   , wherein said transfected myoblasts were provided by an immunocompatible donor.  
     
     
         11 . The method of    claim 8   , wherein said gene encoding a metalloprotease is the metalloprotease-1 gene.  
     
     
         12 . The method of    claim 8   , wherein said gene encoding a metalloprotease is the metalloprotease-2 gene.