Can Short Tags Stop scFv Proteins From Clumping?

Summary. Researchers at the Gwangju Institute of Science and Technology in South Korea reported in Biomacromolecules, published online on 14 October, short Charge-Laden Elastin-like Polypeptide-based Aggregation Reduction (CLEAR) tags tested on two aggregation-prone scFv-based Albubody proteins. Protein aggregation limits how well engineered proteins can be manufactured and stored. Negatively charged variants, particularly CLEAR-E9, kept aggregation indices low for up to 28 days, and after 7 days at 37 °C the two tagged proteins retained about 100% and 95% of their day-0 soluble protein, compared with 87% and 40% for the untagged versions.

Research context (RUO). Size-exclusion chromatography still showed soluble higher-order association, which the authors read as the tag limiting progression toward large insoluble aggregates rather than preventing intermolecular association altogether. A 1.34 kDa variant, CLEAR-E3, also kept a low aggregation index in one construct, and CLEAR-E9 gave higher soluble yield and a lower aggregation index than polyE9 and SynIDP3 control tags. The paper is a protein-engineering and storage-stability study on the tested scFv-based systems. It does not report a clinical programme or any recommendation for use in people. For protein-expression and biophysics laboratories, the contribution is a short, sequence-programmable tag design documented with stability data; full methods are in the open-access article.