Pharmaceutical protein production by transgenic chickens: several viewpoints towards the next stage

Several pharmaceuticals produced by transgenic chickens, Kanuma and Epovet, are already in commercial use, which indicates the potential cost competitiveness of this approach as an "animal bioreactor." Since the establishment of reliable cultivation and genetic modification methods for chicken primordial germ cells, the robustness of this system has increased significantly. Moreover, even proteins that might otherwise be deleterious if expressed systemically may be produced when their expression is restricted to the oviduct through the use of tissue-specific promoters. In this review, we discuss several critical issues that must be addressed in order to advance chicken bioreactor systems to the next stage. First, glycosylation profiles should be optimized according to the intended application. Although chickens generally exhibit mammalian-like glycosylation patterns, egg white proteins are known to carry relatively short glycans that lack terminal galactose and sialic acid residues. Therefore, technologies enabling the introduction of appropriate glycan structures need to be developed. Second, the screening process for establishing transgenic lines should be minimized to reduce overall production costs. Recent advances in site-specific genome modification technology are promising in this regard, provided that patent disputes can be resolved. The integration of these emerging strategies into transgenic chicken bioreactor platforms could further enhance their competitiveness as systems for recombinant protein production.