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Giovanni Magistrelli Yves Poitevin Florence Schlosser Guillemette Pontini Pauline Malinge Soheila Josserand 《MABS-AUSTIN》2017,9(2):231-239
When production of bispecific antibodies requires the co-expression and assembly of three or four polypeptide chains, low expression of one chain can significantly limit assembly and yield. κλ bodies, fully human bispecific antibodies with native IgG structure, are composed of a common heavy chain and two different light chains, one kappa and one lambda. No engineering is applied to force pairing of the chains, thus both monospecific and bispecific antibodies are secreted in the supernatant. In this context, stoichiometric expression of the two light chains allows for maximal assembly of the bispecific antibody. In this study, we selected a κλ body with suboptimal characteristics due to low kappa chain expression. Codon optimization to increase expression of the kappa chain did not improve bispecific yield. Surprisingly, progressive introduction of non-optimal codons into the sequence of the lambda chain resulted in lowering its expression for an optimal tuning of the relative distribution of monospecific and bispecific antibodies. This codon de-optimization led to doubling of the κλ body yield. These results indicate that assembly of different proteins into a recombinant complex is an interconnected process and that reducing the expression of one polypeptide can actually increase the overall yield. 相似文献
293.
Soheila Haddad J. Kent Pollock William T. Phillips Herbert A. Pohl 《Journal of biological physics》1985,13(3):74-78
Readily discernable changes in electrical character take place during the division cycle of the yeast,Saccharomyces cerevisiae. By using the technique of cellular spin resonance, the electrical polarizability of individual cells can be seen to change with the life cycle, as determined by cell morphology. The polarizability changes indicate that during the advance through the life cycle, the ionic double layers associated with the outer cell wall gradually tighten. 相似文献
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