CNS gene delivery by retrograde transport of recombinant replication-defective adenoviruses

The ability to program recombinant gene expression in specific sets of motor and sensory neurons would facilitate the treatment of a number of acquired and inherited central nervous system (CNS) diseases. In this report, we demonstrate that intramuscular injection of replication-defective recombinant adenovirus results in high-level recombinant gene expression, specifically in the CNS motor and sensory neurons that innervate the inoculated muscles. Neural expression of the recombinant genes results from virus transport into the CNS, presumably by retrograde axonal transport. This novel method of neural gene delivery may be of value in studies designed to improve understanding and treatment of inherited and acquired neurological diseases.