Atherosclerosis, the cause of most age-related heart attacks and strokes, is thought to result from the accumulation of cholesterol and in particular toxic oxysterols in the arterial lining. The quantitatively, and possibly also qualitatively most important oxysterol is 7-ketocholesterol (7KC). Thus, 7KC is justly designated as the major target of medical bioremediation. So far, LysoSENS has focused on discovering microbial enzymes capable of degrading 7KC, and one such enzyme was found. In the meantime, other groups have characterized several further enzymes degrading 7KC in different ways.

None of the groups with 7KC degrading enzymes seem interested in applying their enzymes in a model of atherosclerosis (but the esterase groups do). Furthermore, there is no evidence of collaboration among any of the groups. Thus, it seems prudent for SENS Foundation to synthesize the individual efforts, prepare the application of all these enzymes in unified models of atherosclerosis, and evaluate them competitively and synergistically.

We have added N-glycosylation sites and lysosomal targeting tags to genes that code for five known 7KC degrading enzymes. When expressed in a yeast cell system, and targeted to the endoplasmic reticulum, these sites should receive oligomannose or paucimannose cores.  This should generate appropriate localization in macrophages, giving them the ability to degrade 7KC.