Beyond Starch: Towards a Scalable Potato Platform for Molecular Farming.

Thirty-five years after the first recombinant protein was produced in potato and 30 years after clinical trials of edible vaccines from its tubers, the crop is being reconsidered as a molecular farming chassis. Potatoes can accumulate recombinant proteins in tubers, enabling long-term storage and simplified logistics. Clonal propagation, access to minitubers and microtubers, and an established production infrastructure further distinguish the platform. Limited pollen dispersal and reliance on vegetative propagation also provide biosafety advantages. Despite these features, potato lost ground to other hosts due to low expression levels, high downstream processing (DSP) costs in water- and starch-rich tissues and limited scalability relative to seed-propagated crops. We review the technical and economic factors behind this decline and assess new opportunities to overcome them. Recent advances include refined expression cassettes, ER and secretory pathway engineering (including targeted glycoengineering), multigene stacking, genome editing and enzyme-assisted DSP. Seed-propagated diploid potatoes and alternative Solanum germplasm offer additional chassis options. Together with the emergence of start-ups revisiting potato as a production platform, these advances point to practical routes for re-evaluating its role in plant molecular farming. We argue that a rationally engineered, diploid-based 'bioreactor potato' could complement existing hosts and re-establish relevance in specific niches of next-generation biomanufacturing.