Innate immune response induced by gene delivery vectors

Abstract

Gene therapy is a clinical strategy that has the potential to treat an array of genetic and nongenetic diseases. Vectors for gene transfer are the essential tools of gene therapy. For gene therapy to be successful, an appropriate amount of the therapeutic gene must be delivered into the target cells without substantial toxicity. A major limitation of the use of gene therapy vectors is the innate immune responses triggered by systemic administration of such vectors. It is essential to overcome vector-mediated innate immune responses, such as production of inflammatory cytokines, the maturation of antigen-presenting cells and tissue damage, because the induction of these responses not only shortens the period of gene expression but also leads to serious side effects. Viral vectors (for example, adenovirus (Ad) vectors) have been assumed to be more potent in inducing innate immune responses in spite of their high transduction efficiency since they contain pathogenic proteins. However, recent studies have demonstrated that not only viral vectors but also nonviral vectors, such as lipoplex (liposome/plasmid DNA complex), can induce innate immune responses. Indeed, nonviral vectors including lipoplex induce comparable or larger levels of innate immune response than viral vectors. In this review, we present an overview of the innate immune responses induced by Ad vector and lipoplex, which are used primarily for in vivo gene transfer.