Local gene knockdown in the brain using viral-mediated RNA interference

Jonathan Hommel, Robert M. Sears, Dan Georgescu, Diana L. Simmons, Ralph J. DiLeone

Research output: Contribution to journalArticle

298 Citations (Scopus)

Abstract

Conditional mutant techniques that allow spatial and temporal control over gene expression can be used to create mice with restricted genetic modifications. These mice serve as powerful disease models in which gene function in adult tissues can be specifically dissected. Current strategies for conditional genetic manipulation are inefficient, however, and often lack sufficient spatial control. Here we use viral-mediated RNA interference (RNAi) to generate a specific knockdown of Th, the gene encoding the dopamine synthesis enzyme tyrosine hydroxylase, within midbrain neurons of adult mice. This localized gene knockdown resulted in behavioral changes, including a motor performance deficit and reduced response to a psychostimulant. These results underscore the potential of using viral-mediated RNAi for the rapid production and testing of new genetic disease models. Similar strategies may be used in other model species, and may ultimately find applications in human gene therapy.

Original languageEnglish (US)
Pages (from-to)1539-1544
Number of pages6
JournalNature Medicine
Volume9
Issue number12
DOIs
StatePublished - Dec 2003
Externally publishedYes

Fingerprint

Gene Knockdown Techniques
Viral RNA
RNA Interference
Brain
Genes
RNA
Gene therapy
Gene encoding
Tyrosine 3-Monooxygenase
Gene expression
Neurons
Dopamine
Inborn Genetic Diseases
Genetic Models
Tissue
Mesencephalon
Genetic Therapy
Testing
Enzymes
Gene Expression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hommel, J., Sears, R. M., Georgescu, D., Simmons, D. L., & DiLeone, R. J. (2003). Local gene knockdown in the brain using viral-mediated RNA interference. Nature Medicine, 9(12), 1539-1544. https://doi.org/10.1038/nm964

Local gene knockdown in the brain using viral-mediated RNA interference. / Hommel, Jonathan; Sears, Robert M.; Georgescu, Dan; Simmons, Diana L.; DiLeone, Ralph J.

In: Nature Medicine, Vol. 9, No. 12, 12.2003, p. 1539-1544.

Research output: Contribution to journalArticle

Hommel, J, Sears, RM, Georgescu, D, Simmons, DL & DiLeone, RJ 2003, 'Local gene knockdown in the brain using viral-mediated RNA interference', Nature Medicine, vol. 9, no. 12, pp. 1539-1544. https://doi.org/10.1038/nm964
Hommel, Jonathan ; Sears, Robert M. ; Georgescu, Dan ; Simmons, Diana L. ; DiLeone, Ralph J. / Local gene knockdown in the brain using viral-mediated RNA interference. In: Nature Medicine. 2003 ; Vol. 9, No. 12. pp. 1539-1544.
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