De Novo Design of a Potent Wnt Surrogate Specific for the Frizzled7 Subtype Members

Researchers have developed a potent and specific Wnt surrogate targeting the Frizzled7 (Fzd7) receptor subtype, which is part of a family of receptors involved in cell signaling. This surrogate is composed of three modules: a Fzd7 binder, an LRP6 binder, and a homodimeric protein. It shows strong binding affinity (KD < 2.3 nM) for Fzd7 and closely related subtypes (Fzd1, Fzd2) without affecting other Fzd receptors. The surrogate successfully induced organoid formation from intestinal stem cells and promoted full hair follicle regeneration and robust hair growth in mice. This approach could be used to design Wnt surrogates for specific Fzd receptors, aiding in development, differentiation, organoid cultures, and targeted regeneration.