- Discovered by the Mirus researchers and collaborators at the University of Wisconsin – Madison
- Relies upon elevating intravascular pressure to physically increase the permeability of the cellular membranes of the blood vessel
- When nucleic acids are injected intravascularly under normal physiological conditions, they are retained within the blood stream because these macromolecules are too large to be transported through the cell membranes.
- Quickly degraded by the nucleases in the blood stream & DNA can pass through the blood vessel wall into adjoining muscle cells before this occurs.
Restricting blood flow and elevating pressure are key in delivering plasmid DNA tissue sites
Intravenous (“IV”) delivery of plasmid DNA (“pDNA”) to targeted limb muscle:
- Blood flow in an arm or leg temporarily occluded by a tourniquet
- A pDNA solution is rapidly injected intravenously
- The elevated pressure within the occlusion zone, making the blood vessel wall more permeable and allowing the pDNA to migrate into the adjoining muscle cells
- Blood flow is then restored to normal within a few minutes, with no adverse affects to the vasculature.
Intravenous Nucleic Acid Delivery
to leg muscle.
to leg muscle.
- Once pDNA resident in muscle cells, the introduced DNA produces therapeutic proteins that can be active locally or secreted systemically. If the DNA encodes an antigenic protein, either antibody or cellular immune responses may be induced
- A single dose can result in long-term gene expression, and the ease of repeat administration makes this platform technology ideal for treating chronic illnesses.
- This versatile platform has potential utility to treat a wide range of diseases, including muscular dystrophy, peripheral vascular ischemia, arthritis, anemia, multiple sclerosis, and cancer.
- Preclinical work is ongoing to determine optimum dose levels, dosing frequency, plasmid construction, etc. for use in human clinical studies, the first of which are anticipated in 2005
- Mirus is actively exploring its wide range of uses, as well as investigating protocol modifications that would enable delivery to additional tissues such as joints and bone.
