Mitigating Clonal Variation in Recombinant Mammalian Cell Lines

Jae Seong Lee, Helene Faustrup Kildegaard, Nathan E Lewis, Gyun Min Lee*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


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.
Original languageEnglish
JournalTrends in Biotechnology
Issue number9
Pages (from-to)931-942
Number of pages12
Publication statusPublished - 2019


  • cell line development
  • clonal variation
  • rational cell engineering
  • transgene integration

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