Global non-viral gene transfer to the primate brain following intravenous administration

Mol Ther. 2003 Jan;7(1):11-8. doi: 10.1016/s1525-0016(02)00018-7.

Abstract

Expression plasmids encoding either luciferase or beta-galactosidase were encapsulated in the interior of an "artificial virus" comprised of an 85 nm pegylated immunoliposome, which was targeted to the rhesus monkey brain in vivo with a monoclonal antibody (MAb) to the human insulin receptor (HIR). The HIRMAb enables the liposome carrying the exogenous gene to undergo transcytosis across the blood-brain barrier and endocytosis across the neuronal plasma membrane following intravenous injection. The level of luciferase gene expression in the brain was 50-fold higher in the rhesus monkey as compared to the rat. Widespread neuronal expression of the beta-galactosidase gene in primate brain was demonstrated by both histochemistry and confocal microscopy. This approach makes feasible reversible adult transgenics in 24 hours.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Blood-Brain Barrier
  • Brain / metabolism*
  • Endocytosis
  • Gene Transfer Techniques*
  • Luciferases / genetics
  • Macaca mulatta
  • Microscopy, Confocal

Substances

  • Antibodies, Monoclonal
  • Luciferases