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Biotechnol Lett ; 41(8-9): 929-939, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31321593

RESUMO

OBJECTIVE: To develop a simple robust methodology of screening multiple CHO cell clones secreting recombinant proteins to assess their specific productivity. RESULTS: We developed a dual assay based on immunoassay measurements of a recombinant protein expression combined with staining of viable cells with resazurin. Following this approach, colonies can be simultaneously assessed for cell growth rate and for production of a recombinant protein. Combination of these two assays enables to estimate productivity of a recombinant protein per cell from the very early stages of a cell line development process (CLD) and exclude poor producers from further steps. Comparison of the dual assay with a standard CLD protocol followed by only analysis of protein expression level showed at least 10-20% increase in the amount of clones that can be included into pool of high-producers at early stages. This shortens duration of a typical CLD scheme from 23 to 19 weeks. CONCLUSIONS: Our method: (i) allows to include into workflow clones that demonstrate slow growth during single cell cloning but producing high amounts of a target protein, which otherwise would be lost in standard protocols of cells screening; (ii) can be applied for testing of DNA vectors for transfection and protein production; (iii) can be used for monitoring the heterogeneity of cell population and analysis of stable pools productivity.


Assuntos
Biotecnologia/métodos , Células CHO , Proliferação de Células , Técnicas Citológicas/métodos , Programas de Rastreamento/métodos , Proteínas Recombinantes/metabolismo , Animais , Cricetulus , Proteínas Recombinantes/genética , Coloração e Rotulagem/métodos
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