Bacteriophage: From Bacteria to a Successful Targeted Systemic Gene Delivery for Cancer

Gene delivery to cancer has been hindered by inefficacy of vectors delivered via the systemic route. The use of bacteriophages (phage) in targeting strategies is an attractive alternative. The power of phage display-mediated targeting to the tumor vasculature has also been combined with the integration of genomic cis elements of adeno-associated virus (AAV2), resulting in eukaryotic/prokaryotic hybrid vectors termed AAV/phage (AAVP). To facilitate targeting of cancer cells as well as associated endothelium, the well-established double cyclic RGD (CDCRGDCFC, termed RGD4C) motif, which binds to α v integrin receptors upregulated in the angiogenic blood vessels of tumors, was displayed on the bacteriophage capsid. As a proof of concept, the tissue specificity and efficiency of transgene delivery and expression after systemic administration was confirmed using several animal models of cancer. In vivo imaging of reporter genes was performed using bioluminescence imaging and positron emission tomography. This chapter highlights the potential of tumor-targeted AAVP vector to enhance the effectiveness of systemic gene therapy and genetic imaging modalities.