Systemic delivery of therapeutic viruses.

The treatment of certain diseases will require the systemic delivery of therapeutic genes or viruses. In most cases, intravascular injection is the best delivery method to achieve the systemic distribution of viruses and to enable these agents to reach distant therapeutic sites. However, viruses administered by intravascular injection encounter overlapping barriers that impede their ability to reach their targets, including interactions with blood cells, blood factors and endothelial cells, loss to hepatocytes and macrophages, and destruction by innate and adaptive immune responses. In this review, recent advances in the understanding of the mechanisms determining virus tropism following systemic administration and the pharmacology of therapeutic viruses are described. Adenoviruses are used as a paradigm of these interactions, and factors affecting their therapeutic efficacy and side effects are discussed, as well as how the barriers that impede their ability to reach their targets translate to other therapeutic viruses.