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. 2016 Apr 25;113(19):5245–5250. doi: 10.1073/pnas.1525388113

Fig. 1.

Fig. 1.

Targeting EPO to RBC precursors with a chimeric activator. (A, Top) Chimeric activator schematic illustrating a targeting element (light blue) tethered by a linker (black circles) to a mutated activity element (red, black X = mutation). The chimeric activator initially binds (bold arrow) a target cell receptor (dark blue) via the targeting element, whereas the mutated activity element has a low affinity (dashed arrow) for its own receptor (pink). (A, Middle) Increased local concentration of the activity element overcomes its receptor-binding deficit and facilitates interaction (bold arrow). (A, Bottom) This interaction results in signaling via the activity receptor (bold arrow). (B) On off-target cells lacking a receptor for the targeting element, the activity element has little effect (dashed arrow), owing to its mutation. (C) Schematic molecular model of 10F7-EPOR150A showing the 10F7 scFv bound to huGYPA and EPO binding to EPO-R. (D) Predicted expression pattern of EPO-R (pink) and huGYPA (blue) on RBCs during erythropoiesis, illustrating a period of expression overlap in the bone marrow.