{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T11:04:38Z","timestamp":1783940678630,"version":"3.55.0"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The global epidemic of diabetes mellitus the limitations of current therapies-including waning efficacy, adverse effects, and inability to modify disease progression-have accelerated the shift from conventional pharmacotherapy toward biologic agents. This review examines the emergence of single-chain variable fragments (scFv) as a versatile and engineerable class of biotherapeutics for precision diabetes management. Distinguished from full-length monoclonal antibodies (mAbs) by their compact size, enhanced tissue penetration, and modular design, scFv enable precise targeting of both autoimmune and metabolic pathways underlying type 1 diabetes and type 2 diabetes. We summarize advances in scFv applications spanning immunomodulation (e.g., via CTLA-4 and PD-1) and metabolic regulation (e.g., through insulin-degrading enzyme and GLP-1 receptor). Furthermore, we highlight the unique value of avian-derived scFv in recognizing conserved epitopes and overcoming immune tolerance, along with engineering strategies-such as Fc fusion, PEGylation, and multispecific formatting-that enhance pharmacokinetics and therapeutic efficacy. The clinical success of antibodies like Teplizumab underscores the translational potential of antibody-based platforms. Looking forward, scFv-based biologics, particularly when integrated with humanized Fc domains and half-life extension technologies, offer a promising and customizable strategy for next-generation diabetes therapy, bridging innovative drug design with clinically meaningful metabolic and immune modulation.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1809126","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:43:33Z","timestamp":1780551813000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["scFv-based biologics in diabetes: from therapeutic potential to clinical prospects"],"prefix":"10.3389","volume":"17","author":[{"given":"Shikun","family":"Ge","sequence":"first","affiliation":[{"name":"Shandong Key Laboratory of Applied Technology for Protein and Peptide Drugs, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University","place":["Liaocheng, 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