Inducible expression of suicide genes in Leishmania donovani amastigotes

Elodie Ghedin, Hugues Charest, Wen Wei Zhang, Alain Debrabant, Dennis Dwyer, Greg Matlashewski

Research output: Contribution to journalArticlepeer-review

Abstract

This study tests the feasibility of using the A2 gene regulatory system to create a Leishmania cell line in which attenuation is developmentally regulated when the parasite differentiates from promastigotes to amastigotes. The Leishmania donovani- inducible A2 gene regulatory system was used to differentially express in amastigotes two potential suicide genes: a truncated version of the L. donovani 3'-nucleotidase/nuclease expressed in the cytoplasm and the herpes simplex virus thymidine kinase gene. These genes were inserted between A2 noncoding regulatory sequences for up-regulation of expression in amastigotes. The accumulation of toxic products affected L. donovani cell replication and viability both in vitro and in vivo. The inducible expression of toxic gene products represents a valuable tool for the development of safe and effective vaccines.

Original languageEnglish (US)
Pages (from-to)22997-23003
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number36
DOIs
StatePublished - Sep 4 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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