Nonviral and viral gene transfer to the kidney in the context of transplantation

Ariela Benigni, Susanna Tomasoni, Jens Lutz, Susana Amuchastegui, Maurizio C. Capogrossi, Giuseppe Remuzzi

Research output: Contribution to journalArticle

Abstract

Background/Aims: Local modulation of the immune response through genetic manipulation of the graft is an attractive novel approach to overcome the toxicity of immunosuppressive therapy to prevent acute graft rejection. We have previously reported that the cationic polymer polyethylenimine 25k (PEI 25k) transduced reporter genes when injected into the renal artery, but with a low transfection efficiency. Here we compare the risk/benefit profiles of such a nonviral versus a viral technique of gene transfer to the kidney in the context of renal transplantation. Methods: Donor kidneys from Lewis rats were perfused in a closed circuit with an artificial cell-free medium containing PEI 25k complexed to an expression vector coding for the β- galactosidase (β-gal) gene and subsequently transplanted in a syngeneic animal. In a second set of experiments, donor kidneys were injected or perfused with a replication-deficient adenovirus encoding the β-gal gene (AdCMV.βgal; 1 x 109 plaque-forming units) before transplantation. Results: Perfusion of the kidney with PEI 25k/DNA complexes resulted in large areas of hypoperfusion characterized by injured glomeruli and tubuli, capillary thrombosis and accumulation of C3 in glomerular capillaries. Reperfusion of the kidney was achieved by lowering the PEI 25k/DNA ratio, but no detectable transfection was observed. In animals receiving adenovirus, the β-gal activity increased with time and was localized mainly in proximal and distal tubular cells, as documented by β-gal histochemistry and in situ hybridization. A significantly increased expression of β-gal was achieved by perfusion of the kidney with AdCMV.β-gal before transplantion, β-gal staining mainly localizing in proximal and distal tubular cells. Conclusions: Unlike nonviral methods of gene delivery, adenovirus-mediated gene transfer to the kidney offers exciting perspectives for the development of molecular medicine in the field of organ transplantation. Copyright (C) 2000 S. Karger AG, Basel.

Original languageEnglish
Pages (from-to)307-316
Number of pages10
JournalNephron
Volume85
Issue number4
Publication statusPublished - 2000

Keywords

  • β- Galactosidase
  • Adenovirus
  • Cationic polymer
  • Gene transfer
  • Renal transplantation

ASJC Scopus subject areas

  • Nephrology

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