Two Technologies to Modulate the Wnt Pathway: SWAP/ SWEETS

Surrozen is focused on developing uniquely-engineered antibodies that replicate the function of Wnt pathway proteins to help repair tissue damaged by disease. We are able to generate specific pharmacological tools for research and discovery of therapeutics to promote disease-specific tissue regeneration. Importantly, our approach provides a flexible and robust platform that has generated multiple human antibodies that possess either tissue, disease or cell selectivity. We have developed two technologies to modulate the Wnt pathway; Wnt-mimetics (SWAP) and R-spondin-mimetics (SWEETS).

Wnt-mimetics: SWAP

SWAP (Surrozen Wnt signal activating proteins) are designed to mimic the activity of Wnt protein. They are bi-specific full-length human (IgG) antibodies that, like Wnt proteins, directly activate the canonical Wnt-signaling pathway in target tissue. We have established a robust SWAP discovery platform and generated and validated a broad library of SWAPs that have successfully activated Wnt-signaling in vivo.

Like endogenous Wnt (left side), our SWAP technology activates Wnt signaling by binding specific Fzd and Lrp receptors (right side)

Chen et al. Development of Potent, Selective Surrogate WNT Molecules and Their Application in Defining Frizzled Requirements. Cell Chemical Biology, Online, (2020)

R-spondin-mimetics: SWEETS

SWEETS (Surrozen Wnt signal enhancer engineered for tissue specificity) are designed to enhance the body’s response to endogenous, or existing, Wnt protein. They are antibody-based molecules that, like R-spondin, enhance Wnt signaling by stabilizing Frizzled receptors. We have established a robust SWEETS discovery platform and generated hepatocyte-specific SWEETS.

Our SWEETS technology leads to amplification of the Wnt signaling pathway by inhibition of Fzd degradation by the E3 ligase/proteasome pathway. Specificity of SWEETS binding is driven by an antigen-binding domain that can be targeted to specific cell surface proteins

Zhang, et al. Tissue-targeted R-spondin mimetics for liver regeneration. Sci Rep, 10(1):13951 (2020)