Kidney-targeted liposome-mediated gene transfer in mice

L. W. Lai, G. W. Moeckel, Y. H.H. Lien

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

To develop gene therapy targeted to the kidney, we compared three different routes of liposome-mediated gene delivery to the kidney in mice, ie intra-renal-pelvic, intra-renal-arterial, and intra-renal-parenchymal injections. A plasmid construct, pCMVβgal, containing a cytomegalovirus (CMV) immediate-early gene promoter and a β-galactosidase reporter gene was mixed with a 1:1 liposome mixture of N[1-(2,3-dioleoyloxy)propyl]-N, N,trimethylammonium chloride (DOTMA)/dioleoyl phosphatidyl ethanolamine (DOPE). The pCMVβgal-liposome complex was injected into the left kidney via three different routes. The efficacy of gene transfer was assessed using 5-bromo-4-chloro-3-indolyl β-D-galactopyranoside (X-gal) staining on frozen kidney sections 3 to 42 days after injections. Cells with β-galactosidase activity were detected in the cortex and outer medulla in both intra-renal-pelvic and intra-renal-arterial groups, but not in the intra-renal-parenchymal group or in the contralateral noninjected kidney. Evidence of gene transfer was observed only in tubular epithelial cells, but not in glomerular, vascular, or interstitial compartments. The levels of β-galactosidase expression started to decrease 3 weeks after injection. The gene transfer in the kidney was not associated with nephrotoxicity as assessed by blood urea nitrogen levels and renal histology. We conclude that both intra-renal-pelvic and intra-renal-arterial injections provide a transient gene transfer to the renal tubular cells and are suitable routes for kidney-targeted gene therapy.

Original languageEnglish (US)
Pages (from-to)426-431
Number of pages6
JournalGene Therapy
Volume4
Issue number5
DOIs
StatePublished - Jan 1 1997

    Fingerprint

Keywords

  • Gene therapy
  • Kidney
  • Lipofection
  • β-galactosidase

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this