In vivo correction of genetic defects of monocyte/macrophages using attenuated Salmonella as oral vectors for targeted gene delivery

P. Paglia, N. Terrazzini, K. Schulze, C. A. Guzmán, M. P. Colombo

Research output: Contribution to journalArticlepeer-review

Abstract

Macrophages are normal targets for Salmonella during natural infections, and it has been demonstrated that attenuated bacteria can deliver nucleic acid vaccine constructs. Therefore, we assessed if attenuated Salmonella can be used for the in vivo delivery of transgenes to their natural cellular target, in an attempt to correct genetic defects associated with monocytes/macrophages. This system would offer the distinct advantage of achieving a specific targeting of defective cells in a non-invasive form. Using a reporter gene, we demonstrated that attenuated Salmonella could be used as an effective in vitro delivery system to transfer genetic material into nondividing cells like murine macrophages. In vivo, the oral administration of attenuated Salmonella allows targeted delivery of transgenes to macrophages and subsequently expression of transgenes at a systemic level. IFNγ-deficient mice (GKO) were thus selected as a model for the in vivo validation of the Salmonella-based delivery approach. Attenuated Salmonella, used as the carrier for a eukaryotic expression vector encoding the murine IFNγ gene, was able to restore the production of this cytokine in GKO macrophages. Their oral administration to IFNγ-deficient mice also re-established, in these immunocompromised animals, the natural resistance to bacterial infections. These results demonstrate, for the first time, that attenuated Salmonella can be successfully used in vivo as a DNA delivery system for the correction of a genetic defect associated with monocyte/macrophages.

Original languageEnglish
Pages (from-to)1725-1730
Number of pages6
JournalGene Therapy
Volume7
Issue number20
Publication statusPublished - 2000

Keywords

  • Gene therapy
  • GKO mice
  • IFNγ
  • Inherited disease
  • Salmonella

ASJC Scopus subject areas

  • Genetics

Fingerprint

Dive into the research topics of 'In vivo correction of genetic defects of monocyte/macrophages using attenuated Salmonella as oral vectors for targeted gene delivery'. Together they form a unique fingerprint.

Cite this