Issues in the development of gene therapy: Preclinical experiments in E1A gene delivery

We recently completed a phase I trial of EIA gene therapy for patients with advanced breast or ovarian cancers. The trial's rationale was that EIA gen e would downregulate HER-2/neu expression by repressing the gene's transcri ption, thus reversing the malignant phenotype. Our preclinical studies show ed that i) transfection capabilities were not reduced in preparing E1A/cati onic liposome complexes, ii)beta-galactosidase reporter genes could be dete cted in patients' tumor samples after ex viva transfection, and iii) HER-2/ neu gene expression could be quantified by quantitative imaging analysis. T hese results facilitated the translation of our basic research findings int o a clinical trial and to obtain final approval from the National Institute s of Health Recombinant DNA Advisory Committee.