Promoter- and strain-selective enhancement of gene expression in a mouse skeletal muscle by a polymer excipient Pluronic P85

Zhihui Yang, Jian Zhu, Srikanth Sriadibhatla, Catherine Gebhart, Valery Alakhov, Alexander Kabanov

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Amphiphilic triblock copolymers of ethylene oxide and propylene oxide (Pluronic) significantly enhanced expression of plasmid DNA in the skeletal muscle. In the presence of Pluronic P85 (P85) high levels of expression of a reporter gene (luciferase) were sustained for at least 40 days and the area under the gene expression curve increased by at least 10 times compared to the DNA alone. The effect of Pluronic depended on the strain of the mouse and the type of the promoter used. Thus, P85 enhanced luciferase expression by 17 to 19-fold in immunocompetent C57Bl/6 and Balb/c mice, while no enhancement was observed with athymic Balb/c nu/nu mice. Furthermore, P85 activated the expression of luciferase gene driven by CMV promoter, NFκB and p53 response elements. There was much less or no effect on the gene driven by SV40 promoter or AP1 and CRE response elements. Overall, the promoter selectivity suggested that Pluronic induced transcriptional activation of gene expression by activating the p53 and NFκB signaling pathways. In addition Pluronic increased the number of DNA copies and thus affected initial stages of gene transfer in a promoter selective manner.

Original languageEnglish (US)
Pages (from-to)496-512
Number of pages17
JournalJournal of Controlled Release
Volume108
Issue number2-3
DOIs
StatePublished - Nov 28 2005

Keywords

  • Block copolymer
  • Gene expression
  • Inflammation
  • NFκB
  • Plasmid DNA
  • Skeletal muscle
  • Transcription
  • p53

ASJC Scopus subject areas

  • Pharmaceutical Science

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