ArticlePloS one2020
Mitigation of liquid-liquid phase separation of a monoclonal antibody by mutations of negative charges on the Fab surface.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 8 citations in OpenAlex.
- Molecular origins of opalescence and phase separation in mAb formulations and their relation to aggregation.Communications chemistry · 2026Article
- Growth of Clusters toward Liquid-Liquid Phase Separation of Monoclonal Antibodies as Characterized by Small-Angle X-ray Scattering and Molecular Dynamics Simulation.The journal of physical chemistry. B · 2025Article
- Non-specificity as the sticky problem in therapeutic antibody development.Nature reviews. Chemistry · 2022Review
- Antibodies with Weakly Basic Isoelectric Points Minimize Trade-offs between Formulation and Physiological Colloidal Properties.Molecular pharmaceutics · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Some monoclonal antibodies undergo liquid-liquid phase separation owing to self-attractive associations involving electrostatic and other soft interactions, thereby rendering monoclonal antibodies unsuitable as therapeutics. To mitigate the phase separation, formulation optimization is often performed. However, this is sometimes unsuccessful because of the limited time for the development of therapeutic antibodies. Thus, protein mutations with appropriate design are required. In this report, we describe a case study involving the design of mutants of negatively charged surface residues to reduce liquid-liquid phase separation propensity. Physicochemical analysis of the resulting mutants demonstrated the mutual correlation between the sign of second virial coefficient B2, the Fab dipole moment, and the reduction of liquid-liquid phase separation propensity. Moreover, both the magnitude and direction of the dipole moment appeared to be essential for liquid-liquid phase separation propensity, where electrostatic interaction was the dominant mechanism. These findings could contribute to a better design of mutants with reduced liquid-liquid phase separation propensity and improved drug-like biophysical properties.
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