Sonochemical induction of ABCA1 expression and compositions therefor

摘要

The present invention provides compositions useful for transfecting cells (e.g., liver cells) to express ABCA1. The compositions described herein comprise a pharmaceutically acceptable aqueous carrier containing sonochemically-active microspheres together with a plasmid DNA construct encoding an active form of ABCA1 and at least one promoter for the expression thereof. Preferably, the sonochemically-active microspheres comprise, consist essentially of, or consist of gas bubbles (e.g., a fluorocarbon gas, such as octafluoropropane) encapsulated within protein-containing or lipid-containing shells (e.g., human serum albumin shells). The microspheres are disruptable by exposure to ultrasonic acoustic energy to release the encapsulated gas.

主权项

1. A pharmaceutical composition for increasing HDL-cholesterol levels in the blood of a patient, the composition comprising a mixture of a nucleic acid encoding an expressible open reading frame and sonochemically-active microspheres in a pharmaceutically acceptable aqueous carrier; wherein the nucleic acid of the mixture consists of a plasmid vector, the expressible open reading frame consists of an expressible open reading frame encoding the active form of ATP-binding cassette transporter A1 (ABCA1), and the plasmid vector also includes at least one sequence adapted to promote expression of the open reading frame in a mammalian cell; and wherein the sonochemically-active microspheres comprise gas bubbles encapsulated within shells comprising a protein, a lipid, or a combination thereof, the microspheres being disruptable upon exposure to ultrasonic acoustic energy to release the encapsulated gas bubbles; and wherein the composition transfects liver cells when intravenously administered to the patient while ultrasonically imaging the liver, to elicit production of an increased level of HDL-cholesterol in the blood of the patient compared to the HDL-cholesterol level in the blood of the patient prior to administering the composition.