Intravenous delivery of polynucleotides to cells in mammalian limb

A process for delivering molecules to extravascular cells in a mammalian limb comprising;

• a) supplying said molecules in a volume of pharmaceutically acceptable solution of about 0.2 to about 0.6 milliliters of said solution per milliliter of displaced target area volume,
• b) inserting an injection device into a vein in said limb;
• c) forming an occlusion of said vein proximal to an intended site of injection of said polynucleotide;
• and,
• d) injecting said solution into said vein in an antegrade direction wherein the volume and rate of injection combine to increase permeability of veins and venules in said limb and increase the volume of extravascular fluid in said target area thereby delivering said molecules to said extravascular cells in said limb distal to said occlusion.

A process for delivering siRNA polynucleotides or siRNA-expressing polynucleotides to extravascular cells in a primate limb comprising:

• a) supplying said polynucleotides in a volume of pharmaceutically acceptable solution of about 0.2 to about 0.6 milliliters of said solution per milliliter of displaced target area volume,
• b) inserting an injection devise into a vein;
• c) forming an occlusion of said vein proximal to an intended site of injection of said polynucleotides;
• and,
• d) rapidly injecting said solution into said vein in an antegrade direction wherein the volume and rate of injection combine to increase permeability of veins and venules in said limb and increase the volume of extravascular fluid in said target area thereby delivering said polynucleotides to said extravascular cells in said limb distal to said occlusion.