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Designed transmembrane helices that interfere with the new interface, delivered with mRNA technology, selectively block ligand-independent but not ligand-dependent signaling. Our study provides a conceptual framework for understanding and repairing disease-causing TMD mutations of single-pass cytokine receptors.<\/jats:p>","DOI":"10.1073\/pnas.2601748123","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:59:57Z","timestamp":1777399197000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Structural rewiring of IL-7R dimerization by an oncogenic transmembrane mutation can be reversed by rational design"],"prefix":"10.1073","volume":"123","author":[{"given":"Qian","family":"Wang","sequence":"first","affiliation":[{"name":"Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"State Key Laboratory of Chemical Biology, Chinese Academy of Sciences","place":["Shanghai, 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