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Sonochemical induction of ABCA1 expression and compositions therefor

  • US 9,393,328 B2
  • Filed: 06/30/2015
  • Issued: 07/19/2016
  • Est. Priority Date: 03/14/2013
  • Status: Active Grant
First Claim
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1. A method for increasing HDL-cholesterol levels in the blood of a subject, the method comprising the steps of:

  • (a) intravenously co-administering to the subject a plasmid vector encoding the active form of ATP-binding cassette transporter A1 (ABCA1), and sonochemically-active microspheres;

    wherein the vector comprises an expressible open reading frame encoding the active form of ABCA1 and 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;

    (b) ultrasonically imaging a tissue of the subject to be transfected by the plasmid while the plasmid and microspheres are circulating through the vasculature of the tissue and thereby detecting the presence of the microspheres in the vasculature of the tissue; and

    (c) while the microspheres are present in the tissue, applying pulses of ultrasonic energy to the tissue at an acoustical energy level higher than a level required for imaging and at a sufficient energy level to disrupt the microspheres and release the gas bubbles therefrom, the pulses of ultrasonic energy and release of gas bubbles thereby temporarily increasing the porosity of cells in the tissue to facilitate entry of the plasmid into the cells;

    wherein the plasmid transfects the cells and elicits production of an increased level of HDL-cholesterol in the blood of the subject compared to the HDL-cholesterol level in the blood of the subject prior to administering the plasmid.

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