INDUCIBLE EXPRESSION OF SUICIDE GENES IN LEISHMANIA-DONOVANI AMASTIGOTES

This study tests the feasibility of using the A2 gene regulatory syste m to create a Leishmania cell line in which attenuation is development ally regulated when the parasite differentiates from promastigotes to amastigotes. The Leishmania donovani- inducible A2 gene regulatory sys tem was used to differentially express in amastigotes two potential su icide genes: a truncated version of the L. donovani 3'-nucleotidase/nu clease expressed in the cytoplasm and the herpes simplex virus thymidi ne kinase gene. These genes were inserted between A2 noncoding regulat ory sequences for up-regulation of expression in amastigotes. The accu mulation of toxic products affected L. donovani cell replication and v iability both in vitro and in vivo. The inducible expression of toxic gene products represents a valuable tool for the development of safe a nd effective vaccines.