Recombinant viruses and their use for treatment of atherosclerosis and other forms of coronary artery disease and method, reagent, and kit for evaluating susceptibility to same

Abstract

Recombinant viruses comprising a heterologous DNA sequence coding for a lipase involved in lipoprotein metabolism. The invention also concerns the preparation and use in therapy of said recombinant viruses, especially for the treatment or prevention of dyslipoproteinemia-related pathologies.

1 - 15 . (canceled)  
     
     
         16 . A defective recombinant adenovirus comprising a nucleic acid sequence coding for a biologically active lipoprotein lipase (LPL), wherein the nucleic acid sequence is placed under the control of a signal permitting its expression in an infected cell.  
     
     
         17 . The defective recombinant adenovirus according to  claim 16 , wherein the nucleic acid sequence is a cDNA sequence.  
     
     
         18 . The defective recombinant adenovirus according to  claim 16 , wherein the nucleic acid sequence codes for human LPL.  
     
     
         19 . The defective recombinant adenovirus according to  claim 16 , wherein the expression signal is a viral promoter.  
     
     
         20 . The defective recombinant adenovirus according to  claim 19 , wherein the expression signal is selected from the group consisting of E1A, MLP, CMV, and RSV LTR promoters.  
     
     
         21 . A defective recombinant adenovirus comprising a cDNA sequence coding for a biologically active lipoprotein lipase (LPL) under the control of an RSV LTR promoter.  
     
     
         22 . The defective recombinant adenovirus according to  claim 16 , wherein the virus further comprises a nucleic acid sequence enabling the lipoprotein lipase to be directed into a pathway of secretion in an infected cell.  
     
     
         23 . The defective recombinant adenovirus according to  claim 22 , wherein the secretion sequence is the native secretion sequence of lipoprotein lipase.  
     
     
         24 . The defective recombinant adenovirus according to  claim 16 , wherein the virus lacks the regions of its genome which are needed for its replication in a target cell.  
     
     
         25 . The defective recombinant adenovirus according to  claim 16 , wherein the virus is selected from the group consisting of human adenovirus type Ad 2, human adenovirus type Ad 5, and canine adenovirus type CAV-2.  
     
     
         26 . The defective recombinant adenovirus according to  claim 25 , further comprising a gene coding for an apolipoprotein.  
     
     
         27 . The defective recombinant adenovirus according to  claim 26 , wherein the apolipoprotein is selected from the group consisting of ApoA-I and ApoA-IV.  
     
     
         28 . A defective recombinant adenovirus comprising a nucleic acid sequence coding for hepatic lipase and further comprising a nucleic acid sequence coding for apolipoprotein selected from the group consisting of ApoA-I and ApoA-IV, wherein the nucleic acid sequences are placed under the control of a signal permitting their expression in an infected cell.  
     
     
         29 . A composition comprising the defective recombinant adenovirus according to  claim 16  and a pharmaceutically acceptable vehicle.  
     
     
         30 . The composition according to  claim 29 , wherein the composition is in an injectable form.  
     
     
         31 . The composition according to  claim 29 , comprising between 10 4  and 10 10  pfu/ml of defective recombinant adenoviruses.  
     
     
         32 . A mammalian cell infected 16 in vitro with the defective recombinant adenovirus according to claim, whereby a biologically active lipoprotein lipase is expressed from the defective recombinant adenovirus.  
     
     
         33 . The mammalian cell according to  claim 32 , wherein the cell is a human cell.  
     
     
         34 . The mammalian cell according to  claim 33 , wherein the cell is selected from the group consisting of a fibroblast, myoblast, hepatocyte, endothelial cell, glial cell, and keratinoctyte.  
     
     
         35 . A composition comprising the infected mammalian cell according to  claim 32  and an extracellular matrix.  
     
     
         36 . The composition according to  claim 35 , wherein the extracellular matrix comprises a gelling compound selected from the group consisting of collagen, gelatin, glycosaminoglycans, fibronectin, and lectins.  
     
     
         37 . The composition according to  claim 35 , wherein the extracellular matrix comprises a support permitting anchorage of the infected cell.  
     
     
         38 . The composition according to  claim 37 , wherein the support comprises polytetrafluoroethylene fibers.