Compostions and methods for enabling cholesterol catabolism in human cells
AssigneeNational Institute of Health (NIH), U.S. Dept. Of Health and Human Services (DHHS), U.S. Government
InventorsRichard Eric Honkanen, Brandon Marshall D'Arcy, Mark Raymond Swingle
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Abstract
Compositions, methods, and systems for modifying sterol metabolism in a subject is disclosed. In some embodiments, the subjects may be administered one or more mammalian cells modified to express at least one sterol degrading enzyme derived from a bacterium. In many embodiments, the cell is a macrophage or monocyte stably expressing three or more enzymes that aid in opening the β ring of cholesterol. The disclosed compositions and methods may be useful in lowering cholesterol levels in a subject in need thereof. In some embodiments, the subject may have a genetic predisposition to atherosclerosis.
Claims17
A nucleic acid composition comprising:
- a coding sequence, coding for one or more proteins selected from humanized forms of cholesterol dehydrogenase (coded for by nucleotides 166 to 1284 of SEQ ID NO:10;
- CholD), 3-ketosteroid Δ1-dehydrogenase (coded for by nucleotides 170 to 1704 of SEQ ID NO:13;
- Δ1-KstD), anoxic cholesterol metabolism B enzyme (coded for by nucleotides 74 to 1756 of SEQ ID NO:11;
- acmB), 3-ketosteroid 9α-hydroxylase (coded for by nucleotides 132 to 1316 and 1416 to 2483 of SEQ ID NO:17;
- KshAB), 3β-hydroxysteroid dehydrogenase 2 (coded for by nucleotides 3554 to 4672 of SEQ ID NO:12;
- HSD2), and a fusion protein of P450-ferredoxin reductase-ferredoxin fusion (SEQ ID NO:5;
- P450-FdxR-Fdx);
- and
- a control sequence, for regulating the transcription of one or more of the coding sequences in a eukaryotic cell.
Dependencies are inferred from the claim text.