SR-BI regulatory sequences and therapeutic methods of use

Multicellular living organisms and unmodified parts thereof and – Nonhuman animal – Transgenic nonhuman animal

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800 21, 435 6, 435 29, 4353201, 435325, 536 241, 536 2431, 935 6, 935 36, C12N 500, C12N 1500, C07H 2104

Patent

active

059657901

ABSTRACT:
The invention features nucleic acid molecules that are involved with (e.g. activate or regulate) human SR-BI receptor transcription, as well as complements thereto, and homologs thereof. In addition, drug discovery assays are provided for identifying agents which modulate SR-BI promoter activity and thereby modulate the expression of a gene regulated thereby. Such agents can be useful therapeutically for treating or preventing the development of a disease or condition that is caused or contributed to by an aberrant SR-BI activity. In a preferred embodiment, the disease or condition is characterized by inappropriate lipid transfer or metabolism (e.g., atherosclerosis or gallstone formation). Such agents can also be used to modulate expression of a specific gene under the control of the SR-BI promoter in gene therapy. Moreover, the present invention provides diagnostic assays and reagents for determining whether a subject has a disorder involving, for example, aberrant expression of SR-BI genes.

REFERENCES:
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Acton, S. et al. "Identification of Scavenger Receptor SR-BI as a High Density Lipoprotein Receptor" Science 271:518-520, 1996.
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Calvo, D. et al. "The CD36, CLA-1 (CD36L1), and LIMPII (CD36L2) Gene Family: Cellular Distribution, Chromosomal Location, and Genetic Evolution" Genomics 25:10-106, 1995.
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Rigotti, A. et al. "The Class B Scavenger Receptors SR-BI and CD36 are Receptor for Anionic Phospholipids" J. Biol. Chem. 270 (27):16221-16224, 1995.
Tang, Y. et al. "Identification of a Human CD36 Isoform Produced by Exon Skipping" J. Biol. Chem 269 (8):6011-6015, 1994.
Wang, N. et al. "Scavenger Receptor BI (SR-BI) is up-regaulated in adrenal gland in apolipoprotein A-I and hepatic lipase knock-out mice as a response to deplation of cholesterol stores" J. Biol. Chem 271 (35):21001-21004, 1996.

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