Peripheral infection with adenovirus causes unexpected long-term brain inflammation in animals injected intracranially with first-generation, but not with high-capacity, adenovirus vectors: toward realistic long-term neurological gene therapy for chronic diseases.

摘要: Although adenoviral vectors provide prolonged gene expression in the brain by comparison to peripheral organs, is eliminated a severe inflammatory infiltration (i.e., activated macrophages/microglia and T-lymphocytes) after infection with adenovirus. Here, we demonstrate that high-capacity (HC-Ad) succeed maintaining long-term transgene brain, even presence of an active immunization adenovirus completely eliminates from first-generation within 60 days. Importantly, days infection, brains injected exhibited evidence chronic CD8+ cells, macrophage/microglial activation, up-regulation MHC-I expression. No inflammation was observed HC-Ad vector. Thus, these results will allow safe, stable, This markedly improves prospects for use therapy neurological disorders.