Roche Madison Inc.

Mirus Bio Corporation

Julia Hegge

Jon Asher Wolff

James E Hagstrom

Vladimir G Budker

Hans Herweijer

Vladimir M Subbotin

Sean D Monahan

David L Lewis

Tatyana Budker, Legal Representative

Mark Noble

James E Hangstrom

An intravenous delivery method is described that enables delivery of polynucleotides to extravascular cells of a mammalian limb. The method involves the injection of polynucleotides into a distal vein of a limb that is transiently occluded. Polynucleotide delivery is facilitated by rapid injection in sufficient volume to enable extravasation of the solution into surrounding tissue.

Intravenous delivery of polynucleotides to cells in mammalian limb

A process for delivering a polynucleotide to a cardiac tissue cell in a mammal is described, comprising introducing a composition consisting of a polynucleotide into a blood vessel and increasing permeability of the blood vessel to the polynucleotide. The polynucleotide can be a small interfering RNA or microRNA and inhibit gene expression in the cell.

Process for delivering sirna to cardiac muscle tissue

Disclosed is a system for providing in vivo delivery of molecules or complexes to extravascular mammalian cells using an intravascular administration route. The molecules or complexes are inserted in an injection solution into a mammalian vasculature. Insertion of the injection solution at an appropriate rate transiently increases the volume of extravascular fluid in the tissue thereby facilitating delivery of the molecule to the cell.

Delivery of molecules and complexes to mammalian cells in vivo

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.

Nucleic acid injected into hepatic vein lumen

Disclosed is a process for providing for expression of an exogenous nucleic acid in an extravascular parenchymal cell of a mammal. The nucleic acid is inserted into a vessel of a mammal and the permeability of the vessel is increased. Increasing permeability of the vessel allows delivery of the nucleic acid to an extravascular parenchymal cell.

Intravascular delivery of nucleic acid

Disclosed is a system for providing in vivo delivery of polynucleotides to mammalian prostate cells using an intravascular administration route. The polynucleotides are inserted in an injection solution into a mammalian vasculature. Insertion of the injection solution at an appropriate rate increases the volume of extravascular fluid in the tissue thereby facilitating delivery of the polynucleotide to the cell.

Process for delivery of polynucleotides to the prostate

A process is described for the delivery of a therapeutic polynucleotide to limb muscle tissue suffering from or potentially suffering from ischemia. The polynucleotide is inserted into a mammalian limb vessel such as an artery. Delivery efficiency and distribution is enhanced by combining injection of a solution containing the polynucleotide with the use of an externally applied cuff.

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Monona, WI, United States of America

Julia Hegge