Multiplex transcript analysis for identifying high-producing cell lines

BIOT 241

Christina J Lee, leec@gene.com, Gargi Seth, Joni Tsukuda, and Robert W Hamilton. Early Stage Cell Culture, Genentech, Inc, 1 DNA Way, MS 32, San Francisco, CA 94080
Chinese hamster ovary cells are used as hosts for the production of therapeutic recombinant proteins. However, the current process of selecting high-producing clones is both time-consuming and labor-intensive. Improved methods of clone screening are required to meet increasing demands for efficient and streamlined production processes. In particular, we examined the potential of using antibody transcript levels as criteria for two aspects of clone screening: selecting for high-producing clones and identifying clones with questionable product quality. We used QuantiGene® Plex (Panomics, Inc., Fremont, CA), a high-throughput, high-sensitivity assay for measuring multiple transcripts from cell lysate, to enhance our current process of clone screening. Using the development of stable cell lines as examples, we investigated the relationship between transcript and protein levels through several rounds of screening. First, we observed that measured heavy chain expression levels are correlated with specific productivity, enabling the identification of high-producing clones from mRNA. Second, we observed that low ratios of light to heavy chain expression levels may be indicative of product aggregation levels, allowing us to rapidly identify and eliminate 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.
 

Poster Session
5:30 PM-7:30 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biochemical Technology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007