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A clone screening method using mRNA levels to determine specific productivity and product quality for monoclonal antibodies
Author(s) -
Lee Christina J.,
Seth Gargi,
Tsukuda Joni,
Hamilton Robert W.
Publication year - 2008
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.22126
Subject(s) - chinese hamster ovary cell , clone (java method) , monoclonal antibody , antibody , biology , immunoglobulin light chain , microbiology and biotechnology , messenger rna , cell culture , computational biology , gene , biochemistry , genetics
To meet increasing demands for efficient and streamlined production processes of therapeutic antibodies, improved methods of screening clones are required. In this article, we examined the potential of using antibody transcript levels as criteria for clone screening. We evaluated the QuantiGene Plex, a commercially available, high‐throughput assay for simultaneously measuring multiple transcripts from cell lysate. Using the development of stable Chinese hamster ovary cell lines as examples, we investigated the relationship between transcript and antibody levels through several rounds of screening. First, we observed that measured heavy chain transcript levels are generally correlated with specific productivity, enabling the identification of high‐producing clones from mRNA. Second, we observed that low ratios (<1.5) of light to heavy chain transcript levels may be indicative of high antibody aggregation levels, allowing for the rapid identification and elimination of clones of questionable product quality. Therefore, an efficient process of identifying high‐producing clones of desirable product quality is possible by using QuantiGene Plex assay to measure antibody transcript levels. Biotechnol. Bioeng. 2009;102: 1107–1118. © 2008 Wiley Periodicals, Inc.