Engineering ENB-0040
A subcutaneous enzyme replacement therapy with affinity for bone that is currently in clinical trials.ENB-0040 is an engineered, bone-targeted form of recombinant human TNSALP (see figure). Soluble human TSNALP
A molecule that catalyzes or triggers biochemical reactions.enzyme is fused to the Fc portion of human IgG (the binding portion of the Also known as immunoglobulins, these molecules are found in blood or other bodily fluids and are used by the immune system to identify and neutralize foreign substances, such as bacteria and viruses.antibody Immunoglobulin G) that is then linked to a deca-aspartate bone-targeting peptide derived from A glycoprotein that is abundant in bone mineral matrix and has been implicated as an important factor in bone remodeling.osteopontin and A component of mineralized tissues such as bone, dentine, cementum, and calcified cartilage.bone sialoprotein, two key proteins naturally targeted to bone.
With a high affinity for bone, the enzyme is designed to efficiently exert effect at the bone with limited systemic impact. A distribution study has shown that ENB-0040’s half-life was 30% longer in bone compared to serum.
Left Panel shows a Scanning Electron Microscope of ENB-0040 bound to hydroxyapatite crystals. To allow SEM visualization the enzyme was stained with Protein-A coated colloidal-gold particles which binds strongly to the Fc region of ENB-0040. Right panel (control) shows that Protein-A gold by itself does not bind to hydroxyapatite.