Compositions, methods, and apparatus for delivery of a macromolecular assembly to an extravascular tissue of an animal
First Claim
1. A composition for delivering a macromolecular assembly having a diameter not greater than about 1 micrometer to an extravascular tissue of an animal, the composition comprising the macromolecular assembly and a vascular permeability-enhancing agent, wherein the vascular permeability-enhancing agent is not conjugated with a macromolecule.
3 Assignments
0 Petitions
Accused Products
Abstract
Compositions, methods, and an apparatus are provided for delivering a macromolecular assembly such as a plasmid, virus vector, or other gene vector, to an extravascular tissue such as muscle tissue. The composition comprises the macromolecular assembly and a vascular permeability-enhancing agent. In another embodiment, the composition further comprises a vasodilating agent. The method of the invention comprises providing a vascular permeability-enhancing agent to a blood vessel and providing a macromolecular assembly to the vessel. An oxygenator useful for providing oxygen to a fluid extracorporeally prior to providing the fluid to a blood vessel of an animal is included in the invention.
77 Citations
44 Claims
- 1. A composition for delivering a macromolecular assembly having a diameter not greater than about 1 micrometer to an extravascular tissue of an animal, the composition comprising the macromolecular assembly and a vascular permeability-enhancing agent, wherein the vascular permeability-enhancing agent is not conjugated with a macromolecule.
- 9. A kit for providing a macromolecular assembly to an extravascular tissue of an animal, the kit comprising a vascular permeability-enhancing agent and a vasodilating agent, wherein the vascular permeability-enhancing agent is not conjugated with a macromolecule.
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16. A method of delivering a macromolecular assembly to an extravascular tissue of an animal, the method comprising
providing a vascular permeability-enhancing agent to a blood vessel associated with the extravascular tissue to increase the permeability of the endothelial layer of the vessel, wherein the vascular permeability-enhancing agent is not conjugated with a macromolecule, and providing the macromolecular assembly to the vessel, whereby the assembly is delivered to the extravascular tissue through the endothelial layer of the vessel.
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33. A method of delivering a gene vector to an extravascular tissue of an animal, the method comprising
a) isolating a blood vessel associated with the tissue from the blood circulatory system of the animal; - thereafter
b) providing a vasodilating agent to the vessel;
thereafterc) providing a vascular permeability-enhancing agent to the vessel to increase the permeability of the endothelial layer of the vessel;
providing the gene vector to the vessel, whereby the vector is delivered to the extravascular tissue through the endothelial layer of the vessel;
increasing the perfuision pressure within the vessel above the normal physiological perfusion pressure; and
providing an oxygen-transporting agent to the vessel; and
thereafterd) providing a clearance solution to the vessel, the clearance solution being substantially free of the vascular permeability-enhancing agent.
- thereafter
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34. A method of providing a gene vector to substantially all muscle tissues of an animal, the method comprising
a) subjecting the animal to extracorporeal circulatory support and oxygenation; - and thereafter
b) providing a vasodilating agent to the blood circulatory system of the animal;
providing a vascular permeability-enhancing agent to the blood circulatory system to increase the permeability of the endothelial layer of the vessels of the blood circulatory system;
providing the gene vector to the blood circulatory system, whereby the vector is delivered to substantially all muscle tissues through the endothelial layer of the vessels of the blood circulatory system; and
increasing the perfusion pressure within the vessel above the normal physiological perfusion pressure.
- and thereafter
Specification