An AAV promoter-driven neuropeptide Y gene delivery system using Sendai virosomes for neurons and rat brain

P. Wu, C. M. De Fiebre, W. J. Millard, M. A. King, S. Wang, S. O. Bryant, Y. P. Gao, E. J. Martin, E. M. Meyer

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

An adeno-associated virus (AAV)-derived construct (pJDT95npy) containing rat neuropeptide Y (NPY) cDNA inserted downstream of endogenous AAV promoters was used to investigate AAV-driven NPY expression in post-mitotic neurons in vitro and in the brain. NPY mRNA was expressed in NT2/N and rat brain primary neuronal cultures after transfection. There was a corresponding increase in the number of neurons staining for NPY-like immunoreactivity and an increase in NPY release during depolarization in the primary cultures. Injections of Sendai-virosome encapsulated pJDT95npy into neocortex increased NPY-like immunoreactivity in neurons but not glia indicating that the latter cell type did not have the translational, post-translational or storage capacity to accumulate the peptide. Injections into the rat hypothalamic paraventricular nucleus increased body weight and food intake for 21 days, though NPY-like immunoreactivity remained elevated for at least 50 days. These studies demonstrate that AAV-derived constructs may be useful for delivering genes into post-mitotic neurons, and that Sendai virosomes are effective for delivering these constructs in vivo.

Original languageEnglish (US)
Pages (from-to)246-253
Number of pages8
JournalGene Therapy
Volume3
Issue number3
StatePublished - Mar 1 1996
Externally publishedYes

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Keywords

  • Adeno-associated virus
  • Brain
  • Feeding behavior
  • Virosome
  • Y

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Wu, P., De Fiebre, C. M., Millard, W. J., King, M. A., Wang, S., Bryant, S. O., Gao, Y. P., Martin, E. J., & Meyer, E. M. (1996). An AAV promoter-driven neuropeptide Y gene delivery system using Sendai virosomes for neurons and rat brain. Gene Therapy, 3(3), 246-253.