Nucleic acid injected into hepatic vein lumen
Processes are described for obtaining high levels of gene expression in primates after injection of nucleic acid to the liver via the lumen of the hepatic vein. The described process results in high level of gene expression with transient increases in liver enzymes.
1. A process for delivering a polynucleotide to a liver cell in a mammal, comprising:
a) forming an occlusion in a hepatic vessel in said mammal; and,
b) injecting the polynucleotide in a solution into the lumen of said hepatic vessel.
2. The process of claim 1 wherein the hepatic vessel consists of a hepatic vein.
3. The process of claim 1 wherein the hepatic vessel consists of a hepatic artery.
4. The process of claim 1 wherein the hepatic vessel consists of a portal vein.
5. The process of claim 1 wherein the hepatic vessel consists of a bile duct.
6. The process of claim 1 further comprising occluding a hepatic vein.
7. The process of claim 1 further comprising forming occlusions in one or more efferent or afferent hepatic blood vessels.
8. The process of claim 1 further comprising suppressing the immune system of said mammal.
9. The process of claim 1 wherein the solution is injected at a rate of 18 ml/kg/min or greater.
10. The process of claim 1 wherein the solution is injected at a rate of 36 ml/kg/min or greater.
11. The process of claim 1 wherein the solution is injected at a rate of 48 ml/kg/min or greater.
12. The process of claim 1 wherein the injection of the solution results in vessel pressure of 10 mm Hg or greater.
13. The process of claim 1 wherein the injection of the solution results in vessel pressure of 45 mm Hg or greater.
14. The process of claim 1 wherein the injection of the solution results in vessel pressure of 105 mm Hg or greater.
15. The process of claim 1 wherein the polynucleotide is selected from the group consisting of naked DNA, viral vector and non-viral vector.
16. The process of claim 1 wherein the polynucleotide is selected from the group consisting of blocking polynucleotide, antisense nucleic acid, siRNA, plasmid, and expression vector.
17. A process for delivering a polynucleotide to a liver cell in a mammal, comprising:
a) forming an occlusion in a hepatic vessel in said mammal;
b) injecting the polynucleotide in a solution into the lumen of said hepatic vessel;
c) removing said occlusion; and,
d) repeating the injection procedure of steps a, b, and c one or more times.