Targeted gene therapy for rat glomerulonephritis using HVJ-immunoliposomes

J Gene Med. Sep-Oct 2002;4(5):527-35. doi: 10.1002/jgm.300.

Abstract

Background: Kidney targeted gene transfer has been attempted by many researchers over the last 10 years; however, unfortunately, no reliable technique for gene transfer to the kidney has been established. At experimental level several in vivo gene transfer methods have been reported.

Methods: We were the first to report successful in vivo gene transfer into the kidney using the HVJ-liposome method. Since then, this method has been modified to achieve highly efficient gene transfer. In this study, we have developed a renal glomerulus-specific gene transfer method using HVJ-liposomes with anti-Thy 1 antibody, OX-7.

Results: Following systemic delivery of fluoroisothiocyanate (FITC)-labeled oligodeoxynucleotides (ODN) by HVJ-liposomes coupled with OX-7, we observed fluorescence in renal glomeruli from 2 h post-administration. To examine the efficacy of this delivery system, NF-kappaB or scrambled (SD) decoy ODN was administered by HVJ-liposomes coupled with OX-7 into a crescent glomerulonephritis, anti-glomerular basement membrane (GBM) model. Animals given SD decoy ODN developed severe glomerulonephritis by day 7 with heavy albuminuria, glomerular crescent formation and up-regulated renal expression of IL-1beta and ICAM-1. In contrast, NF-kappaB decoy ODN treatment substantially inhibited the disease with a reduction in alubuminuria, histological damage and the renal expression of inflammatory cytokines.

Conclusions: This study has demonstrated that systemic delivery of HVJ-liposomes coupled with OX-7 results in efficient ODN transfer in rat glomeruli. NF-kappaB, but not SD decoy ODN administered systemically via HVJ-liposomes complexed with OX-7 showed clear therapeutic potential for glomerulonephritis. This novel ODN transfer method combined with decoy strategy has the potential to lead to the establishment of a new therapeutic approach to glomerular diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Carriers*
  • Genetic Therapy*
  • Glomerulonephritis / genetics*
  • Glomerulonephritis / therapy*
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Liposomes
  • NF-kappa B / metabolism
  • Rats
  • Sendai virus*

Substances

  • Drug Carriers
  • Liposomes
  • NF-kappa B