ApoB-derived receptor-binding domains facilitate recombinant protein delivery into egg yolk.

Proteins that accumulate in egg yolk are typically enriched in terminal sialylation, a feature that enhances protein stability and makes the yolk a favorable environment for the production of therapeutic recombinant proteins. However, to date, efficient strategies for directing recombinant proteins into the yolk remain limited. Aside from approaches involving fusion to the Fc region of human immunoglobulin G (IgG), no broadly applicable method has been established to effectively accumulate recombinant proteins within the egg yolk. Here, we designed a yolk-targeting peptide (YT peptide) composed of the apolipoprotein B (ApoB)-derived proteoglycan-binding and low-density lipoprotein receptor (LDLR)-binding domains and investigated its ability to facilitate receptor-mediated delivery of recombinant proteins into egg yolk. Recombinant proteins fused with the YT peptide were systemically administered to laying quail, and their accumulation in egg yolk was evaluated. Fusion proteins containing the YT peptide showed markedly enhanced deposition in egg yolk compared with control proteins lacking the YT peptide, as confirmed by fluorescence imaging and western blot analysis. These findings indicate that the YT peptide enhances the deposition of recombinant proteins into egg yolk and support its future evaluation as a module for yolk-directed protein delivery in stable avian expression systems.