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Design principles and therapeutic applications of novel synthetic WNT signaling agonists

Authors :
Yorick Post
Chenggang Lu
Russell B. Fletcher
Wen-Chen Yeh
Huy Nguyen
Sung-Jin Lee
Yang Li
Source :
iScience, Vol 27, Iss 6, Pp 109938- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Summary: Wingless-related integration site or Wingless and Int-1 or Wingless-Int (WNT) signaling is crucial for embryonic development, and adult tissue homeostasis and regeneration, through its essential roles in cell fate, patterning, and stem cell regulation. The biophysical characteristics of WNT ligands have hindered efforts to interrogate ligand activity in vivo and prevented their development as therapeutics. Recent breakthroughs have enabled the generation of synthetic WNT signaling molecules that possess characteristics of natural ligands and potently activate the pathway, while also providing distinct advantages for therapeutic development and manufacturing. This review provides a detailed discussion of the protein engineering of these molecular platforms for WNT signaling agonism. We discuss the importance of WNT signaling in several organs and share insights from the initial application of these new classes of molecules in vitro and in vivo. These molecules offer a unique opportunity to enhance our understanding of how WNT signaling agonism promotes tissue repair, enabling targeted development of tailored therapeutics.

Details

Language :
English
ISSN :
25890042
Volume :
27
Issue :
6
Database :
Directory of Open Access Journals
Journal :
iScience
Publication Type :
Academic Journal
Accession number :
edsdoj.51fbdba0cc7644558da5ecd67f417121
Document Type :
article
Full Text :
https://doi.org/10.1016/j.isci.2024.109938