Comparison of transduction efficiency of recombinant AAV serotypes 1, 2, 5, and 8 in the rat nigrostriatal system

Nikolaus R. McFarland, Jeng Shin Lee, Bradley T. Hyman, Pamela J. McLean

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Enhanced delivery and expression of genes in specific neuronal systems is critical for the development of genetic models of neurodegenerative disease and potential gene therapy. Recent discovery of new recombinant adeno-associated viral (rAAV) capsid serotypes has resulted in improved transduction efficiency, but expression levels, spread of transgene, and potential toxicity can differ depending on brain region and among species. We compared the transduction efficiency of titer-matched rAAV 2/1, 2/5, and 2/8 to the commonly used rAAV2/2 in the rat nigrostriatal system via expression of the reporter transgene, enhanced green fluorescent protein. Newer rAAV serotypes 2/1, 2/5, and 2/8 demonstrated marked increase in transduction and spread of enhanced green fluorescent protein expression in dopaminergic nigrostriatal neurons and projections to the striatum and globus pallidus compared to rAAV2/2 at 2 weeks post-injection. The number of nigral cells transduced was greatest for rAAV2/1, but for serotypes 2/5 and 2/8 was still two- to threefold higher than that for 2/2. Enhanced transduction did not cause an increase in glial cell response or toxicity. New rAAV serotypes thus promise improved gene delivery to nigrostriatal system with the potential for better models and therapeutics for Parkinson disease and other neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)838-845
Number of pages8
JournalJournal of neurochemistry
Issue number3
StatePublished - May 2009


  • Adeno-associated virus
  • Gene therapy
  • Parkinson disease
  • Striatum
  • Substantia nigra
  • Transduction

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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