Kinome-level screening identifies inhibition of polo-like kinase-1 (PLK1) as a target for enhancing non-viral transgene expression

Matthew D. Christensen, Jacob J. Elmer, Seron Eaton, Laura Gonzalez-Malerva, Joshua LaBaer, Kaushal Rege

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Human cells contain hundreds of kinase enzymes that regulate several cellular processes, which likely include transgene delivery and expression. We identified several kinases that influence gene delivery and/or expression by performing a kinome-level screen in which, we identified small-molecule kinase inhibitors that significantly enhanced non-viral (polymer-mediated) transgene (luciferase) expression in cancer cells. The strongest enhancement was observed with several small-molecule inhibitors of Polo-like Kinase 1 (PLK 1) (e.g., HMN-214 and BI 2536), which enhanced luciferase expression up to 30-fold by arresting cells in the G2/M phase of the cell cycle and influencing intracellular trafficking of plasmid DNA. Knockdown of PLK 1 using an shRNA-expressing lentivirus further confirmed the enhancement of polymer-mediated transgene expression. In addition, pairwise and three-way combinations of PLK1 inhibitors with the histone deacetylase-1 (HDAC-1) inhibitor Entinostat and the JAK/STAT inhibitor AG-490 enhanced luciferase expression to levels significantly higher than individual drug treatments acting alone. These findings indicate that inhibition of specific intracellular kinases (e.g., PLK1) can significantly enhance non-viral transgene expression for applications in biotechnology and medicine.

Original languageEnglish (US)
Pages (from-to)20-29
Number of pages10
JournalJournal of Controlled Release
StatePublished - Apr 28 2015


  • BI 2536
  • Cell cycle
  • HMN-214
  • Kinases
  • Polymer Gene Delivery
  • Transient protein expression

ASJC Scopus subject areas

  • Pharmaceutical Science


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