Compositions, kits, methods, and apparatus for transvascular delivery of a composition to an extravascular tissue of a mammal

Abstract

Compositions, methods, kits, and 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 proving 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 a mammal is included in the invention. Kits, apparatus, and methods for using the catheters described herein for isolating cardiac circulation, diverting caval blood flow from the right atrium, and for other purposes, are also described.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS [0001] This application is a continuation of co-pending U.S. application Ser. No. 09 / 597,890 filed 19 Jun. 2000, which is now (allowed) and a continuation of U.S. application No. PCT / US98 / 27072 filed 18 Dec. 1998 (now abandoned), and is entitled to priority pursuant to 35 U.S.C. 119(e) to U.S. provisional patent application 60 / 068,317, which was filed on 19 Dec. 1997.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] This work was supported in part by a grant from the U.S. Government (NIH Grants Nos. P30-DK 47757-03 sub 07 and P01-AR43648-01 sub 04 Project 2) and the U.S. Government may therefore have certain rights in this invention. BACKGROUND OF THE INVENTION [0003] The invention relates generally to the fields of gene therapy and cardiac therapy. [0004] It is well known that viruses naturally deliver nucleic acids to cells and have therefore been exploited as gene delivery vehicles. However, in order for a recombinant ...

AI Technical Summary

Problems solved by technology

Circulating virus in a mammal may not have ready access to cells to which it is desired that a nucleic acid be delivered.

Unfortunately, the position of the heart within the human body has, in the past, required the use of highly invasive procedures for providing therapy directly and locally to cardiac tissue.

In addition to the serious physiological complications which sometimes accompany such highly invasive procedures, these interventions may also exact a high psychological toll from patients who undergo them.

These patients endure the physical trauma and long recovery periods associated with invasive cardiac procedures, and often emerge from recovery scarred, both physically and mentally.

Patients afflicted with cardiac and other myopathies are unable to benefit from many of the improvements being made to gene vectors, and from greater understanding of how their afflictions might be alleviated using gene therapy methods, because of a severe paucity of methods for performing local gene therapy in cardiac and other muscle tissues.

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