biostudies-literatureMakowski EKUniversity of MichiganPfizerNational Institutes of HealthNIGMS NIH HHSNational Science Foundation2146629https://www.ebi.ac.uk/biostudies/studies/S-EPMC9704398biostudies-literatureUnknown14(1)Self-association governs the viscosity and solubility of therapeutic antibodies in high-concentration formulations used for subcutaneous delivery, yet it is difficult to reliably identify candidates with low self-association during antibody discovery and early-stage optimization. Here, we report a high-throughput protein engineering method for rapidly identifying antibody candidates with both low self-association and high affinity. We find that conjugating quantum dots to IgGs that strongly self-associate (pH 7.4, PBS), such as lenzilumab and bococizumab, results in immunoconjugates that are highly sensitive for detecting other high self-association antibodies. Moreover, these conjugates can be used to rapidly enrich yeast-displayed bococizumab sub-libraries for variants with low levels ofmAbsReduction of therapeutic antibody self-association using yeast-display selections and machine learning.PMC97043981T32GM140223-01Rackham Predoctoral FellowshipT32 GM140223Graduate Research FellowshipLambert MZupancic JMMakowski EKTessier PMBennett EMLou WChen HDesai AAGallo CJZhang YTully TSmith MDLin LEschmann NSFernando AfalseReduction of therapeutic antibody self-association using yeast-display selections and machine learning.Self-association governs the viscosity and solubility of therapeutic antibodies in high-concentration formulations used for subcutaneous delivery, yet it is difficult to reliably identify candidates with low self-association during antibody discovery and early-stage optimization. Here, we report a high-throughput protein engineering method for rapidly identifying antibody candidates with both low self-association and high affinity. We find that conjugating quantum dots to IgGs that strongly self-associate (pH 7.4, PBS), such as lenzilumab and bococizumab, results in immunoconjugates that are highly sensitive for detecting other high self-association antibodies. Moreover, these conjugates can be used to rapidly enrich yeast-displayed bococizumab sub-libraries for variants with low levels of2022-01-01T00:00:00Z2022 Jan-Dec2025-05-18T13:23:33.98Z2025-05-18T13:23:33.98ZS-EPMC97043983643373710.1080/19420862.2022.2146629