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

    July 2025 in “ bioRxiv (Cold Spring Harbor Laboratory) ”
    Junyup Lee, Y. S. Bae, Tae-Keun Jeong, Seok‐Min Yun, Jeeyoon Chang, Sung Gwe Ahn, Hyeop-Jo Han, Jungho Mun, Seung Jun Kim, Ho Min Kim, Dae‐Sik Lim, Yoon Ki Kim, Eui‐Jeon Woo, Hanseul Yang, Ho‐Chul Shin, Bo-Seong Jeong, Byung‐Ha Oh
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    Studysummary This study developed a potent Wnt surrogate with high specificity for the Fzd7 receptor in mice, promoting full hair follicle regeneration and robust hair growth, suggesting potential applications in tissue development and targeted regeneration.
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    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.
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