Technologies

The inventors have disclosed the engineering and purification of a recombinant S1P chaperone, called ApoM (Apolipoprotein M) fusion product. It contains the ApoM domain covalently linked to the N-terminus of IgG1-Fc, and serves as an excellent means of delivering S1P, which can be used to reduce hypertension.

Technology Overview
Endothelial cells play a key role in vascular diseases. Plasma high-density lipoprotein (HDL) strongly supports endothelial cell function. However, only certain species of HDL are useful in this regard. Specifically, Apolipoprotein M-containing HDL (ApoM ⁺ HDL) that carries the bioactive lipid S1P, can activate G-protein coupled S1P receptors, thereby suppressing inflammatory responses. Therefore, ApoM is thought to function as an S1P chaperone. S1P is vital for health since decreased plasma S1P levels were observed in coronary artery disease, diabetes, and myocardial infarctions among others.

The inventors have described a method to engineer and purify a fusion protein called ApoM-Fc that contains the ApoM moiety covalently linked to the IgG1-Fc. This fusion product serves as a safe and effective means of delivering S1P to endothelial cells. The inventors found thatin vivo, the fusion protein could raise plasma levels of S1P and deliver S1P to various organs. The fusion product could also reduce experimental hypertension in animals for at least 7 days.In vitro, the fusion product could activate S1P receptors.