Mammalian expression platforms are primary production systems for therapeutic proteins that require complex post-translational modifications. Current processes used for developing recombinant mammalian cell lines generate clonal cell lines with high phenotypic heterogeneity, which has puzzled researchers that use mammalian cell culture systems for a long time. Advances in mammalian genome-editing technologies and systems biotechnology have shed light on clonal variation and enabled rational cell engineering in a targeted manner. We propose a new approach for a next-generation cell line development platform that can minimize clonal variation. Combined with the knowledge-based selection of ideal integration sites and engineering targets, targeted integration-based cell line development will allow tailored control of recombinant gene expression with predicted phenotypes.
- cell line development
- clonal variation
- rational cell engineering
- transgene integration
Lee, J. S., Kildegaard, H. F., Lewis, N. E., & Min Lee, G. (2019). Mitigating Clonal Variation in Recombinant Mammalian Cell Lines. Trends in Biotechnology, 37(9), 931-942. https://doi.org/10.1016/j.tibtech.2019.02.007