![]() We also introduce a methodology for controlled release of heterologous proteins from the spore core, which utilises components of the PBSX prophage to lyse spores during germination and outgrowth. Lysates from physically disrupted spores are shown to stimulate differentiation of a pre-adipocyte cell line to mature adipocyte cells, indicating that the spore-core located human growth hormone is folded correctly and functional. The method is exemplified by the expression and deposition of human growth hormone in the developing spore core, where the protein is shielded from physicochemical and biological degradation by the protective spore structure. Here we extend the concept by engineering spores intended as oral delivery vehicles for therapeutic proteins. Methodologies that exploit the durability of Bacillus subtilis spores by displaying heterologous proteins or antigenic molecules on the spore surface for mucosal vaccine delivery and other applications are well established.
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