Covert Warfare Against the Immune System: Decoy Capsids, Stealth Genomes, and Suppressors

Abstract

In part owing to their low immune profile, adeno-associated virus (AAV) vectors have long been viewed as ideal for in vivo gene transfer. They are based on a small, nonpathogenic virus that is composed of a single-stranded DNA genome and a protein capsid. As compared with many other viral vectors, recombinant AAVs are better at avoiding activation signals, are less efficient in transducing professional antigen-presenting cells, and elicit weaker and more transient innate inflammatory responses.1 Ultimately, these naturally stealthy vectors have been able to express various transgenes for months if not years in numerous immune-competent animal models. Many serotypes with differing tropism that are capable of transducing various cell types in vivo have been identified. Induction of immune tolerance to transgene products has been demonstrated for hepatic gene transfer, which induces regulatory T cells (Tregs).2,3