Evolving Phage Vectors for Cell Targeted Gene Delivery - An Update

Bacteriophage vectors are an attractive alternative to synthetic and animal viral gene delivery vectors. We have demonstrated that ligand targeted bacteriophage particles can be used to deliver a functional transgene to mammalian cells that bear the appropriate receptors. Because transduction of mammalian cells by untargeted phage is negligible, the specificity of phage-mediated gene delivery can be determined by the choice of targeting ligand that is displayed on the phage surface. Thus, phage display vectors can potentially be targeted genetically for gene delivery to specific cells in the body with little or no delivery to non-targeted cells. Moreover, since bacteriophage have not evolved to replicate in mammalian cells they are not likely to have toxicity problems associated with many animal viral vectors. Although the efficiency of phage-mediated gene delivery has been low compared to animal viral vectors, studies demonstrating increased gene transfer using agents that stimulate DNA repair indicate the potential for improving phage-mediated gene delivery. Indeed, the same principles of phage display that have been applied extensively to the directed evolution of binding ligands can now be applied to the adaptation of the phage particles, themselves for safe and effective therapeutic gene delivery.