Neuron-restrictive silencer elements mediate neuron specificity of adenoviral gene expression

Neuron-restrictive silencer elements (NRSEs) were used to target the gene e xpression of adenoviral vectors specifically to neuron cells in the central nervous system. By generating adenoviral constructs in which NRSE sequence s were placed upstream from the ubiquitous phosphoglycerate kinase promoter , the specificity of expression of a luciferase reporter gene was tested in both cell lines and primary cultures. Whereas transgene expression was neg ligible in nonneuronal cells following infection with an adenovirus contain ing 12 NRSEs, neuronal cells strongly expressed luciferase when infected wi th the same adenovirus. The NRSEs restricted expression of the luciferase g ene to neuronal cells in vivo when adenoviruses were injected both intramus cularly into mice and intracerebrally into rats. This NRSE strategy may avo id side effects resulting from the ectopic expression of therapeutic genes in the treatment of neurological diseases. In particular, it may allow the direct transfection of motor neurons without promoting transgene expression within inoculated muscles or the secretion of transgene products into the bloodstream.