Induction of blood vessel formation through administration of polynucleotides encoding sphingosine kinases

Abstract

A method of inducing blood vessel formation in an animal by administering to the animal a polynucleotide encoding a sphingosine kinase, or an analogue, fragment, or derivative thereof. The polynucleotide may be contained in an appropriate expression vector, such as a viral vector. The delivery of sphingosine kinase through administration of an expression vector which expresses sphingosine kinase provides for the formation of larger blood vessels containing a well defined structure that is supported by mural cells such as pericytes and smooth muscle cells.

What is claimed is:  
     
         1 . A method of inducing blood vessel formation in an animal, comprising:administering to said animal an effective amount of a sphingosine kinase, or an analogue, fragment, or derivative thereof.  
     
     
         2 . The method of  claim 1  wherein said sphingosine kinase, or analogue, fragment, or derivative thereof is administered to said animal by administering to said animal a polynucleotide encoding sphingosine kinase, or an analogue, fragment, or derivative thereof.  
     
     
         3 . The method of  claim 2  wherein said polynucleotide encoding a sphingosine kinase, or an analogue, fragment, or derivative thereof is administered to said animal by administering to said animal an expression vehicle including said polynucleotide encoding a sphingosine kinase, or an analogue, fragment, or derivative thereof.  
     
     
         4 . The method of  claim 3  wherein said expression vehicle further includes a polynucleotide encoding a protein selected from the group consisting of VEGF, FGF, IGF, angiopoietins, PD-EGF, TGF-β, HIF1-α, nitric oxide synthase, MCP-1, Interleukin-8, ephrins, NAP-2, ENA-78, GROW-α, and active fragments of tyrosyl-tRNA synthetase.  
     
     
         5 . The method of  claim 3  wherein said expression vehicle is a viral vector.  
     
     
         6 . The method of  claim 5  wherein said viral vector is an adenoviral vector.  
     
     
         7 . The method of  claim 5  wherein said viral vector is a lentiviral vector.  
     
     
         8 . The method of  claim 5  wherein said viral vector is a BIV vector.  
     
     
         9 . The method of  claim 6  wherein said adenoviral vector is administered to said animal in an amount of from about 10 7  plaque forming units to about 10 12  plaque forming units.  
     
     
         10 . The method of  claim 9  wherein said adenoviral vector is administered to said animal in an amount of from about 5×10 8  plaque forming units to about 2×10 11  plaque forming units.  
     
     
         11 . The method of  claim 7  wherein said lentiviral vector is administered to said animal in an amount of from about 5×10 5  transducing units to about 10 12  transducing units.  
     
     
         12 . The method of  claim 11  wherein said lentivirus vector is administered to said animal in an amount of from about 5×10 5  transducing units to about 10 12  transducing units.  
     
     
         13 . The method of  claim 8  wherein said lentiviral vector is administered to said animal in an amount of from about 5×10 5  transducing units to about 10 10  transducing units.  
     
     
         14 . The method of  claim 13  wherein said adenoviral vector is administered to said animal in an amount of from about 5×10 5  transducing units to about 10 10  transducing units.  
     
     
         15 . The method of  claim 1  wherein said animal is a mammal.  
     
     
         16 . The method of  claim 15  wherein said mammal is a primate.  
     
     
         17 . The method of  claim 16  wherein said primate is a human.  
     
     
         18 . A viral vector including a polynucleotide encoding a sphingosine kinase, or an analogue, fragment, or derivative thereof.  
     
     
         19 . The vector of  claim 18  wherein said viral vector further includes a polynucleotide encoding a protein selected from the group consisting of VEGF, FGF, IGF, angiopoietins, PD-EGF, TGF-β, HIF1-α, nitric oxide synthase, MCP-1, Interleukin-8, and ephrins.  
     
     
         20 . The vector of  claim 18  wherein said vector is an adenoviral vector.  
     
     
         21 . The vector of  claim 18  wherein said viral vector is a lentiviral vector.  
     
     
         22 . The vector of  claim 18  wherein said viral vector is a BIV vector.  
     
     
         23 . A method of expressing sphingosine kinase in an animal, comprising: 
 administering to said animal a polynucleotide encoding a sphingosine kinase, or an analogue, fragment, or derivative thereof.    
     
     
         24 . The method of  claim 23  wherein said polynucleotide encoding a sphingosine kinase, or an analogue, fragment, or derivative thereof is administered to said animal by administering to said animal an expression vehicle including said polynucleotide encoding a sphingosine kinase, or an analogue, fragment, or derivative thereof.  
     
     
         25 . The method of  claim 24  wherein said expression vehicle is a viral vector.  
     
     
         26 . The method of  claim 25  wherein said viral vector is an adenoviral vector.  
     
     
         27 . The method of  claim 25  wherein said viral vector is a lentiviral vector.  
     
     
         28 . The method of  claim 25  wherein said viral vector is a BIV vector.  
     
     
         29 . A method for the prevention or the treatment of congestive heart failure in an animal comprising administering to said animal an effective amount of a sphingosine kinase, or an analogue, fragment, or derivative thereof.  
     
     
         30 . A method for the prevention or the treatment of myocardial ischemia in an animal comprising administering to said animal an effective amount of a sphingosine kinase, or an analogue, fragment, or derivative thereof.  
     
     
         31 . A method for the treatment of ischemia-reperfusion injury in an animal comprising administering to said animal an effective amount of a sphingosine kinase, or an analogue, fragment, or derivative thereof.  
     
     
         32 . A method for the treatment of peripheral arterial diseases in an animal comprising administering to said animal an effective amount of a sphingosine kinase, or an analogue, fragment, or derivative thereof.  
     
     
         33 . The method of  claim 29 ,  30 ,  31  or  32  wherein said sphingosine kinase, or analogue, fragment, or derivative thereof is administered to said animal by administering to said animal a polynucleotide encoding sphingosine kinase, or an analogue, fragment, or derivative thereof.  
     
     
         34 . The method of  claim 33  wherein said polynucleotide encoding a sphingosine kinase, or an analogue, fragment, or derivative thereof is administered to said animal by administering to said animal an expression vehicle including said polynucleotide encoding a sphingosine kinase, or an analogue, fragment, or derivative thereof.  
     
     
         35 . The method of  claim 34  wherein said expression vehicle further includes a polynucleotide encoding a protein selected from the group consisting of VEGF, FGF, IGF, angiopoietins, PD-EGF, TGF-β, HIF1-α, nitric oxide synthase, MCP-1, Interleukin-8, and ephrins.  
     
     
         36 . The method of  claim 34  wherein said expression vehicle is a viral vector.  
     
     
         37 . The method of  claim 36  wherein said viral vector is an adenoviral vector  
     
     
         38 . The method of  claim 36  wherein said viral vector is a lentiviral vector.  
     
     
         39 . The method of  claim 36  wherein said viral vector is a BIV vector.  
     
     
         40 . The method of  claim 29 ,  30 ,  31  or  32  wherein said animal is a mammal.  
     
     
         41 . The method of  claim 40  wherein said mammal is a primate.  
     
     
         42 . The method of  claim 41  wherein said primate is a human.