A universal system for boosting gene expression in eukaryotic cell-lines

Inbal Vaknin, Or Willinger, Jonathan Mandl, Hadar Heuberger, Dan Ben-Ami, Yi Zeng, Sarah Goldberg, Yaron Orenstein, Roee Amit

Research output: Contribution to journalArticlepeer-review


We demonstrate a transcriptional regulatory design algorithm that can boost expression in yeast and mammalian cell lines. The system consists of a simplified transcriptional architecture composed of a minimal core promoter and a synthetic upstream regulatory region (sURS) composed of up to three motifs selected from a list of 41 motifs conserved in the eukaryotic lineage. The sURS system was first characterized using an oligo-library containing 189,990 variants. We validate the resultant expression model using a set of 43 unseen sURS designs. The validation sURS experiments indicate that a generic set of grammar rules for boosting and attenuation may exist in yeast cells. Finally, we demonstrate that this generic set of grammar rules functions similarly in mammalian CHO-K1 and HeLa cells. Consequently, our work provides a design algorithm for boosting the expression of promoters used for expressing industrially relevant proteins in yeast and mammalian cell lines.

Original languageEnglish
Article number2394
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2024

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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