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Enhanced Phagemid Particle Gene Transfer in Camptothecin-treated Carcinoma Cells¹

Selective Genetics, Inc., San Diego, California 92121

Engineered phage-based vectors are an attractive alternative strategy for gene delivery because they possess no natural mammalian cell tropism and can be genetically modified for specific applications. Genotoxic treatments that increase the transduction efficiency of single-stranded adeno-associated virus were tested on cells transfected by single-stranded phage. Indeed, green fluorescent protein transgene expression by epidermal growth factor-targeted phagemid particles increased with heat shock, UV irradiation, and camptothecin (CPT) treatment. CPT resulted in transduction efficiencies of 30–45% in certain human carcinoma cell lines and reduced the minimal dose needed to detect green fluorescent protein-expressing cells to as low as 1–10 particles/cell. Targeted phage transduction was effective in many tumor cell lines and in prostate tumor xenografts with CPT treatment. Taken together, these data suggest the feasibility of using phage-based vectors for therapeutic gene delivery to cancer cells.