Perspectives on viral vector design and applications

Publisher Summary This chapter discusses viral vector designs and their applications. Effective human gene therapy depends on the efficient delivery and appropriate expression of therapeutic genes. Attempts to solve the gene delivery problem have used a variety of strategies, including naked DNA, DNA bound by lipids and/or facilitating proteins, and recombinant viruses. Viruses remain attractive as potential gene-delivery vehicles, because they are highly evolved for the invasion of organisms and the delivery of genetic material to cells. Some viruses naturally establish long-term persistence or may express genes in specific cell types. The use of viruses for gene delivery has two obvious drawbacks—namely, (1) most viruses cause disease and (2) many tissues where gene therapy is required are not known to harbor latent or persistent viruses. Although efforts to eliminate viral genes involved in disease have met with considerable success, even viral structural proteins in high concentrations can result in toxicity. Highly mutated viruses can no longer replicate, and thus technology for producing viral vectors by the complementation of defective genes using complementing cells or packaging systems is impeded by low vector yields and contamination with wild-type virus rescuants.