Plants are economical and sustainable factories for the production of recombinant proteins. Currently, numerous proteins produced using different plant-based systems with applications as cosmetic and tissue culture ingredients, research and diagnostic reagents, and industrial enzymes are marketed worldwide. In this study, we aimed to demonstrate the usefulness of a plant-based system to synthesize a single-chain antibody (scFv)-elastin-like polypeptide (ELP) fusion to be applied as an affinity precipitation reagent of the difficult to produce recombinant proteins. We used the human tissue transglutaminase (TG2), the main celiac disease autoantigen, as a proof of concept. We cloned a TG2-specific scFv and fused it to a short hydrophobic ELP tag. The anti-TG2-scFv-ELP was produced in Nicotiana benthamiana and was efficiently recovered by an inverse transition cycling procedure improved by coaggregation with bacteria-made free ELP. Finally, the scFv-ELP was used to purify both plant-synthesized human TG2 and also Caco-2-TG2. In conclusion, this study showed for the first time the usefulness of a plant-based expression system to produce an antibody-ELP fusion designed for the purification of low-yield proteins. K E Y W O R D S affinity precipitation, downstream processing, elastin like polypeptides, molecular farming, single-chain variable antibody fragments 1 | INTRODUCTION Many recombinant proteins produced in plants are currently in the market, such as tissue culture or cosmetic ingredients, research or diagnostic reagents, and industrial enzymes. Less successful has been the production of biopharmaceuticals, with only one approved product and several vaccines in advanced stages of clinical trials (Fischer & Buyel, 2020). Plant-based platforms can compete across different markets due to specific advantages like inexpensive and massively scalable transgenic plant-based systems, or the rapid scaleup of transient leaf expression systems (Fischer & Buyel, 2020). The bottlenecks of molecular farming include the low product yield, the
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