Background: One of the approaches to cancer gene therapy relies on tumor transfection with DNA encoding tox-ins under 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 pTERT-ETA plasmid is highly dependent upon method of preparation of DNA- polyethylenimine complexes. After adjustment of complex preparation protocol cell lines with high ac-tivity of telomerase promoter can be selectively killed by transfection with pTERT-ETA plasmid. We also show 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 a substantial growth retardation of poorly transfectable D2F2/E2 tumor in mice. There were no significant differences in anti-tumor prop-erties between DNA constructs with telomerase or CAG promoters in vivo.