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 language | English |
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Pages (from-to) | 289-296 |
Number of pages | 8 |
Journal | Current Gene Therapy |
Volume | 20 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2020 |
Externally published | Yes |
Keywords
- Gene therapy
- PE40
- Polyethylenimine
- Pseudomonas exotoxin A
- Targeted therapy
- Transfection
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
- Drug Discovery
- Genetics(clinical)