Intravascular delivery of non-viral nucleic acid

Abstract

Disclosed is a complex for providing nucleic acid expression in a cell. A polynucleotide and a polymer are mixed together to form the complex wherein the zeta potential of the complex is not positive. Then the complex is delivered to the cell wherein the nucleic acid is expressed.

1 ) A process for delivering a polynucleotide into an extravascular parenchymal cell of a mammal, comprising: 
 a) inserting the polynucleotide into a mammalian blood vessel, in vivo;    b) increasing the permeability of the blood vessel;    c) passing the polynucleotide through the blood vessel into the extravascular space;    d) delivering the polynucleotide into the mammalian extravascular parenchymal cell; and,    e) expressing the polynucleotide.    
     
     
         2 ) The process of  claim 1  wherein increasing the permeability of the blood vessel consists of increasing pressure against blood vessel walls.  
     
     
         3 ) The process of  claim 2  wherein increasing the pressure consists of increasing a volume of fluid within the blood vessel.  
     
     
         4 ) The process of  claim 3  wherein increasing the volume consists of inserting a solution containing the polynucleotide into the blood vessel.  
     
     
         5 ) The process of  claim 4  wherein increased pressure is controlled by altering the volume of the solution in relation to the time period of insertion.  
     
     
         6 ) The process of  claim 5  wherein the blood vessel consists of a tail vein.  
     
     
         7 ) The process of  claim 1  wherein the cell is selected from the group consisting of a liver cell, spleen cell, heart cell, kidney cell, prostate cell, skin cell, testis cell, skeletal muscle cell, fat cell, bladder cell, brain cell, pancreas cell, thymus cell, and lung cell.  
     
     
         8 ) A process for delivering a polynucleotide complexed with a compound into an extravascular parenchymal cell of a mammal, comprising: 
 a) making a polynucleotide-compound complex wherein the zeta potential of the complex is less negative than the polynucleotide alone;    b) adding another compound to the complex to increase zeta potential negativity of the complex from the previous step;    c) inserting the complex into a mammalian blood vessel;    d) increasing the permeability of the blood vessel;    e) passing the polynucleotide through the blood vessel;    f) delivering the polynucleotide into the mammalian extravascular parenchymal cell; and,    g) expressing the polynucleotide.    
     
     
         9 ) The process of  claim 8  wherein increasing the permeability of the blood vessel consists of increasing pressure against blood vessel walls.  
     
     
         10 ) The process of  claim 9  wherein increasing the pressure consists of increasing a volume of fluid within the blood vessel.  
     
     
         11 ) The process of  claim 10  wherein increasing the volume consists of inserting a solution containing the polynucleotide into the blood vessel.  
     
     
         12 ) The process of  claim 11  wherein a specific volume of the solution is inserted within a specific time period.  
     
     
         13 ) The process of  claim 12  wherein increased pressure is controlled by altering the volume of the solution in relation to the time period of insertion.  
     
     
         14 ) The process of  claim 13  wherein the blood vessel consists of a tail vein.  
     
     
         15 ) The process of  claim 8  wherein the cell is selected from the group consisting of a liver cell, spleen cell, heart cell, kidney cell, prostate cell, skin cell, testis cell, skeletal muscle cell, fat cell, bladder cell, brain cell, pancreas cell, thymus cell, and lung cell.  
     
     
         16 ) The process of claims  1  and  8  wherein the polynucleotide is inserted in at least a 1 milliliter solution.  
     
     
         17 ) The process of claims  1  and  8  wherein the extravascular parenchymal space consists of the hepatocytes.  
     
     
         18 ) The process of  claim 17  wherein intrahepatic parenchymal pressure is at least 10 mm mercury.