Dual-Domain Antibodies with Engineered Fc-FcRn Affinity Modulation

**Molecular Mechanism and Rationale** The neonatal Fc receptor (FcRn), encoded by the FCGRT gene, plays a crucial role in antibody pharmacokinetics through its pH-dependent binding mechanism with immunoglobulin G (IgG) antibodies. Under normal physiological conditions, FcRn binds IgG with high affinity at acidic pH (6.0-6.5) within endosomes and recycling vesicles, while exhibiting minimal binding at neutral pH (7.4) found in plasma and extracellular spaces. This pH-dependent interaction is med...