Non-viral cancer gene therapy: an industrial perspective

Non-viral gene therapy refers to plasmid-based gene delivery systems for the delivery of genes encoding therapeutic proteins to diseased tissue. The genes are encoded on DNA plasmids that are propagated in bacteria. The purified plasmids can be administered by themselves for certain applications or require formulation with synthetic gene delivery systems to increase the level of cellular uptake and ultimately, gene expression. The resultant transfection complex must yield therapeutic levels of the gene product; it must be scaleable for GMP approved pharmaceutical manufacture; it must be safe with regard to toxicity, immunogenicity and recombination; it must have strong intellectual property protection; and manufacture of the product must be cost effective. The present clinical applications of plasmid-based gene therapy technology fulfill most of these requirements for treatment of cancer and cardiovascular disease, and genetic vaccines for infectious diseases. The product candidates are in phase I or phase I/II clinical trials. Results from phase II clinical trials should be available by or shortly into the new millennium. Success with any of these indications will advance the field of plasmid-based gene therapy from a proof-of-concept into a series of pharmaceutical products.