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

Nat Biotechnol. 1999 Sep;17(9):865-9. doi: 10.1038/12849.


Neuron-restrictive silencer elements (NRSEs) were used to target the gene expression of adenoviral vectors specifically to neuron cells in the central nervous system. By generating adenoviral constructs in which NRSE sequences 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 negligible in nonneuronal cells following infection with an adenovirus containing 12 NRSEs, neuronal cells strongly expressed luciferase when infected with the same adenovirus. The NRSEs restricted expression of the luciferase gene to neuronal cells in vivo when adenoviruses were injected both intramuscularly into mice and intracerebrally into rats. This NRSE strategy may avoid 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae Infections / genetics
  • Animals
  • Brain / surgery
  • Female
  • Gene Expression Regulation*
  • Genetic Therapy / methods
  • Genetic Vectors*
  • Injections, Intramuscular
  • Luciferases / genetics
  • Mice
  • Neurons / physiology*
  • PC12 Cells
  • Phosphoglycerate Kinase / genetics
  • Promoter Regions, Genetic
  • Rats
  • Rats, Sprague-Dawley
  • Regulatory Sequences, Nucleic Acid*
  • Tissue Distribution
  • Transgenes


  • Luciferases
  • Phosphoglycerate Kinase