Recombinant adeno viruses comprising an inserted gene encoding apolipoprotein and their use in gene therapy for dyslipoproteinemias

Abstract

The present invention concerns defective recombinant adenoviruses containing an inserted gene encoding apolipoproteins, pharmaceutical compositions comprising the adenovirus, and their use for the treatment or prevention of pathologies linked to dyslipoproteinemias.

We claim:  
     
       1. A replicaton defective recombinant adenovirus comprising an inserted gene encoding human apolipoprotein AI or a natural variant thereof, wherein the inserted gene is under the control of a sequence permitting expression of the gene in a cell. 
     
     
       2. The adenovirus according to  claim 1 , wherein said adenovirus is a type Ad5 adenovirus. 
     
     
       3. The adenovirus according to  claim 1 , wherein the sequence is a CMV or RSV promoter. 
     
     
       4. The adenovirus according to  claim 1 , wherein the inserted gene comprises a signal sequence. 
     
     
       5. A pharmaceutical composition comprising a defective recombinant adenovirus according to  claim 1 . 
     
     
       6. A pharmaceutical composition according to  claim 5 , in injectable form. 
     
     
       7. A pharmaceutical composition according to  claim 5 , comprising between 10 4  and 10 14  pfu/ml of defective recombinant adenovirus. 
     
     
       8. The adenovirus according to  claim 1 , wherein the inserted gene encodes an apolipoproteins AI variant having a cysteine in position 173. 
     
     
       9. A method for the treatment of atherosclerosis comprising administering to an animal an adenovirus of  claim 1 , wherein the gene encoding apolipoprotein AI or a natural variant thereof is expressed at a level effective to inhibit arterial lipid deposition. 
     
     
       10. A pharmaceutical composition according to  claim 7 , comprising between 10 6  to 10 10  pfu/ml of defective recombinant adenovirus. 
     
     
       11. The method according to  claim 9 , wherein the animal is a human. 
     
     
       12. A method for expressing human apolipoprotein AI or a natural variant thereof in a host cell, comprising infecting a host cell with the replication defective recombinant adenovirus according to  claim 1 . 
     
     
       13. The method according to  claim 12 , wherein the host cell is infected in vivo. 
     
     
       14. The method according to  claim 13 , wherein replication defective recombinant adenovirus is injected intravenously. 
     
     
       15. The method according to  claim 14 , wherein the replication defective recombinant adenovirus is injected intravenously via the portal vein. 
     
     
       16. The method according to  claim 12 , wherein the inserted gene encodes an apolipoprotein AI variant having a cysteine in position 173. 
     
     
       17. The method according to  claim 12 , wherein the inserted gene encodes human apolipoprotein AI.