The United States of America, As Represented by the Secretary, Department of Health and Human Services

Aventis Pharma S.a.

Musc Foundation for Research Development

American National Red Cross

Bryan H Brewer

Alan Thomas Remaley

Patrice Denefle

Catherine Prades

Cendrine Lemoine

Fairwell Thomas

Steingrimur P Stefansson

Nicolas Duverger

Stephen J Demosky

John A Stonik

Edward B Neufeld

Marie-Françoise Rosier-Montus

Marcele J A Amar

Laurent Naudin

Sylvia Santamarina-Fojo

William S Argraves

Samar Hammad

Disclosed herein are peptides or peptide analogs with multiple amphipathic &#x3b1;-helical domains that promote lipid efflux from cells via an ABCA1-dependent pathway. Also provided herein are methods of using multi-domain amphipathic &#x3b1;-helical peptides or peptide analogs to treat or inhibit dyslipidemic disorders. Methods for identifying non-cytotoxic peptides that promote ABCA1-dependent lipid efflux from cells are also disclosed herein.

Isolated nucleic acid molecule encoding a peptide or peptide analog comprising the SEQ ID No. 3

The present invention concerns a nucleic acid which is capable of regulating the transcription of the ABC1 gene, which is a causal gene for pathologies linked to a dysfunctioning of cholesterol metabolism, inducing diseases such as atherosclerosis. The invention also relates to nucleotide constructs comprising a polynucleotide which encodes a polypeptide or a nucleic acid of interest, placed under the control a regulatory nucleic acid for the ABC1 gene. The invention also relates to recombinant vectors, transformed host cells and nonhuman transgenic mammals comprising a nucleic acid which regulates the transcription of the ABC1 gene or an abovementioned nucleotide construct, as well as methods for screening molecules or substances which are capable of modifying the activity of the regulatory nucleic acid for the ABC1 gene.

Regulatory nucleic acid for the ABC1 gene, molecules modifying its activity and therapeutic uses

The present invention provides an isolated mammalian receptor which specifically binds a high density lipoprotein holoparticle, comprising a subunit of approximately 45-600 kDa molecular weight and one or more subunits selected from the group consisting of a subunit of approximately 40-50 kDa molecular weight, a subunit of approximately 120 kDa molecular weight and a subunit of approximately 400 kDa molecular weight. In addition, the present invention provides a method of screening a substance for the ability to modulate the HDL holoparticle binding and/or internalization activity of the receptor of this invention, comprising: a) contacting the substance with a cell producing a functional HDL receptor; and b) assaying the cell for a modulation of the HDL holoparticle binding and/or internalization activity of the receptor, whereby a modulation of the HDL holoparticle binding and/or internalization activity of the receptor identifies a substance with the ability to modulate the HDL holoparticle binding and/or internalization activity of the ADL receptor.

Methods and compositions for HDL holoparticle uptake receptor

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Potomac, MD, United States of America

Bryan H Brewer