Growth retardation of poorly transfectable tumor by multiple injections of plasmids encoding pe40 based targeted toxin complexed with polyethylenimine

Yuriy Khodarovich, Darya Rakhmaninova, German Kagarlitskiy, Anastasia Baryshnikova, Sergey Deyev

Research output: Contribution to journalArticlepeer-review

Abstract

Background: One of the approaches to cancer gene therapy relies on tumor transfection with DNA encoding toxins under the control of tumor-specific promoters. Methods: Here, we used DNA plasmids encoding very potent anti-ERBB2 targeted toxin, driven by the human telomerase promoter or by the ubiquitous CAG promoter (pTERT-ETA and pCAG-ETA) and linear polyethylenimine to target cancer cells. Results: We showed that the selectivity of cancer cell killing by the pTERT-ETA plasmid is highly dependent upon the method of preparation of DNA-polyethylenimine complexes. After adjustment of complex preparation protocol, cell lines with high activity of telomerase promoter can be selectively killed by transfection with the pTERT-ETA plasmid. We also showed that cells transfected with pTERT-ETA and pCAG-ETA plasmids do not exert any detectable bystander effect in vitro. Conclusion: Despite this, three intratumoral injections of a plasmid-polyethylenimine complex resulted in substantial growth retardation of a poorly transfectable D2F2/E2 tumor in mice. There were no significant differences in anti-tumor properties between DNA constructs with telomerase or CAG promoters in vivo.

Original languageEnglish
Pages (from-to)289-296
Number of pages8
JournalCurrent Gene Therapy
Volume20
Issue number4
DOIs
Publication statusPublished - 2020
Externally publishedYes

Keywords

  • Gene therapy
  • PE40
  • Polyethylenimine
  • Pseudomonas exotoxin A
  • Targeted therapy
  • Transfection

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery
  • Genetics(clinical)

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