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Application note: Attaining high transient titers in CHO cells
18 January 2016 • Author(s): Chao Yan Liu, Virginia Spencer, Ph.D., Shyam Kumar, Jian Liu, Henry Chiou, Ph.D., and Jonathan F. Zmuda, Ph.D.
Case study involving the use of the ExpiCHO™ mammalian transient expression system
The ability to produce transient CHO derived proteins early during biotherapeutic development is highly desirable to mimic, as closely as possible, the final critical quality attributes of the protein when manufactured at bioproduction scales. Unfortunately, CHO cells typically express lower levels of protein than HEK293 in transient systems, in some instances 50–100 times less than the best 293-based systems, and only modest titer improvements are obtained through the optimisation of individual components of existing transient CHO workflows.
To address the significant unmet need for higher transient CHO protein titers, we employed systems-based approaches whereby the latest advances in cell culture media, feeds, transfection reagents, and expression enhancers were optimised in conjunction with a new high-expressing CHO cell clone.
The goal was to generate a simple and robust workflow for transient protein expression in CHO cells capable of generating gram-perlitre protein titers in 10–14 days, titers previously attainable only by stably expressing cells in a bioreactor setting. These advances allow for unprecedented access to CHO-derived proteins during therapeutic candidate selection and may serve to revolutionise the use of CHO cells for transient protein expression during the early stages of drug development.
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