Folding-mediated secretion of pure bispecific antibodies.

Folding-mediated secretion using ProAla mutations yields highly pure bispecific antibodies with 100% correct pairing in IgG-like formats.

• Why it matters: Producing bispecific antibodies is challenging due to mispairing of chains, which complicates purification and reduces therapeutic efficacy. Improving specificity and purity is crucial for clinical applications.
• What they did: The study engineered ProAla mutations to increase folding energy barriers, ensuring only correctly paired heavy and light chains fold and are secreted, while mispaired chains are retained.
• The result: This approach enhances secretion of pure bsIgGs by preventing mispaired species from being released, enabling more efficient and reliable production of functional bispecific antibodies.