OPGY49R

OPGY49R is a genetically engineered variant of osteoprotegerin (OPG) developed by researchers at the University of Alabama at Birmingham. Wild-type OPG acts as a decoy receptor for receptor activator of NF-κB ligand (RANKL), thereby inhibiting osteoclastogenesis and bone resorption. However, wild-type OPG also binds to TNF-related apoptosis-inducing ligand (TRAIL), which can promote tumor cell survival by blocking TRAIL-induced apoptosis. OPGY49R features a single point mutation (Y49R) that uncouples TRAIL binding while fully retaining its high-affinity binding to RANKL. This allows OPGY49R to prevent osteolytic bone damage and reverse immunosuppression in the tumor microenvironment without interfering with TRAIL-mediated tumor cell apoptosis. It has been investigated in preclinical models of breast cancer bone metastasis, multiple myeloma, and prostate cancer, often delivered via genetically engineered mesenchymal stem cells (MSCs) or recombinant adeno-associated virus (rAAV) vectors.

Other names

OPG Y49ROPG(Y49R)osteoprotegerin Y49Rrecombinant OPGY49R