Composition for transfection of DNA into the liver

Abstract

A composition useful for ultrasound facilitated in vivo transfection of DNA into liver cells of a mammal comprises (a) an ultrasonic contrast agent comprising protein-stabilized gas-filled microspheres, and (b) plasmid DNA encoding apo A1. Preferably, the gass in the microspheres is air, nitrogen oxygen, or a fluorocarbon gas. In some preferred embodiments the DNA encoding apo A1 is operably linked to a promoter.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a division of U.S. Application for patent Ser. No. 10 / 483,189, filed on Aug. 4, 2004, now U.S. Pat. No. 7,211,248, which is the National Stage of International Application Serial No. PCT / US2002 / 21620, filed on Jul. 10, 2002, which claims the benefit of U.S. Provisional Application Ser. No. 60 / 303,784, filed Jul. 10, 2001, each of which is incorporated herein by reference.FIELD OF THE INVENTION [0002] The invention relates to the transfection of DNA into the liver of a mammal, and more particularly relates to the ultrasonic microsphere enhancement of the transfection of DNA into the organs of a mammal, particularly the liver. BACKGROUND OF THE INVENTION [0003] One approach to improve the efficacy of in vivo gene therapy, with the aim at enhancing expression of a transgene, involves utilization of ultrasound to facilitate transfection of DNA into cells. Manome et al., Circulation, 99(20):2617-20(1999), incorporated her...

AI Technical Summary

Benefits of technology

[0020] It is a still further object of the invention to induce apo A1 gene expression by injecting apo A1 genetic material into the liver and enhancing expression of the apo A1 gene using ultrasound and microspheres to facilitate transfection of the apo A1 gene in the liver cells.

[0023] In further embodiments, microspheres or microbubbles are injected into the blood to enhance the transfection process. In a further optional embodiment, increased injection pressure of the DNA or equivalent is applied to enhance the transfection procedure.

Problems solved by technology

7(17):1516-25(2000), reported that gene therapy, as a form of molecular medicine, is expected to have a major impact on medical treatments in the future, but that the clinical use of gene therapy is hampered by inadequate gene delivering systems to ensure sufficient, accurate and safe DNA uptake in the target cells in vivo.

Lawrie noted that progress in cardiovascular gene therapy has been hampered by concerns over the safety and practicality of viral vectors and the inefficiency of current nonviral transfection techniques.