Accession Number : ADA260420


Title :   Chemotherapy of Leishmania with Oligodeoxynucleotide Probes.


Descriptive Note : Final rept.


Corporate Author : MICROPROBE CORP BOTHELL WA


Personal Author(s) : Meyer, Rich B , Jr


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a260420.pdf


Report Date : 14 Feb 1989


Pagination or Media Count : 13


Abstract : The goal of this project has been to investigate the potential of antisense oligonucleotides to kill Leishmania enriettii cells in culture. These antisense oligonucleotides are directed against the 35-base leader sequence spliced to the 5'-end of all Leishmania mRNA, with the objective of achieving cell kill by arresting translation. Agents that successfully arrested growth or killed the parasites in vitro would be viable candidates for study in animal models for treatment of Leishmaniasis, a major problem for American military personnel in certain tropical regions. We have found that mRNA translation can be significantly inhibited by antisense oligonucleotides 20 nucleotides long, and that this is improved by addition of lipophilic or planar aromatic moieties on the 5'-end of the oligonucleotide. These modified oligonucleotides have shown sequence-specific cell killing ability at concentrations at a concentration of 100 micrometers. In this project we have sequenced, for the first time, the spliced leader sequences of L mexicana amazonensis and L braziliensis guyanensis, two species pathogenic to humans, and shown them to be identical to that of L. enriettii. We have also demonstrated that we can arrest translation of mRNA from these species. Oligonucleotide, Antisense, Leishmania, Acridine, Translation, mRNA.


Descriptors :   *MILITARY PERSONNEL , *LEISHMANIASIS , *CHEMOTHERAPY , TISSUE CULTURE CELLS , MODELS , DEOXYRIBONUCLEIC ACIDS , SEQUENCES , CHOLESTEROL , NUCLEOTIDES , DRUG TOLERANCE , ACRIDINES , ANIMALS , TROPICAL REGIONS , PARASITES , CELLS(BIOLOGY) , RIBONUCLEIC ACIDS , CULTURES(BIOLOGY)


Subject Categories : Biochemistry
      Microbiology


Distribution Statement : APPROVED FOR PUBLIC RELEASE