Novel biopharmaceutical strategies: Fc-fusion protein technology.

Therapeutic proteins represent pivotal interventions for diverse pathologies but face inherent limitations, including a short serum half-life and suboptimal stability. Fc-fusion protein technology, an innovative biopharmaceutical approach, conjugates functional protein domains to the IgG Fc fragment via engineered linkers. By exploiting FcRn-mediated recycling and enhanced thermodynamic stability, this strategy extends the circulatory half-life. Concurrently, interactions with FcγRs and complement component 1q (C1q) confer Fc-fusion proteins immunomodulatory functions, for example, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Recent clinical approvals of novel Fc-fusion biologics underscore the translational viability of Fc-fusion proteins. With ongoing innovations in artificial intelligence-guided design and engineered Fc scaffolds, Fc-fusion technology is positioned to dominate next-generation biotherapeutics. Notwithstanding advantages in pharmacokinetics, challenges such as target-mediated drug disposition (TMDD) and FcRn binding interference still need to be addressed. This study systematically evaluates the current status of Fc-fusion protein drugs and recent engineering advancements to enhance the application of Fc-fusion proteins in drug development.