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 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.

Disclosed herein are compositions, constructs, cassettes, vectors, cells, nucleic acids, peptides, proteins, protocols and methods for reducing cholesterol and lipid buildup in mammalian subjects, via gene and/or cell therapeutic treatments. In many embodiments, the disclosed compositions, cells, constructs, cassettes, vectors, nucleic acids, peptides, proteins, protocols and methods may help to reduce lipid levels in mammals. In one embodiment, the disclosed compositions, cells, constructs, cassettes, vectors, nucleic acids, peptides, proteins, protocols and methods are useful in reducing lipid build-up, especially cholesterol, in liver cells.