Document Detail


Antisense phosphorothioate oligonucleotides: selective killing of the intracellular parasite Leishmania amazonensis.
MedLine Citation:
PMID:  8058724     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We targeted the mini-exon sequence, present at the 5' end of every mRNA of the protozoan parasite Leishmania amazonensis, by phosphorothioate oligonucleotides. A complementary 16-mer (16PS) was able to kill amastigotes--the intracellular stage of the parasite--in murine macrophages in culture. After 24 hr of incubation with 10 microM 16PS, about 30% infected macrophages were cured. The oligomer 16PS acted through antisense hybridization in a sequence-dependent way; no effect on parasites was observed with noncomplementary phosphorothioate oligonucleotides. The antisense oligonucleotide 16PS was a selective killer of the protozoans without any detrimental effect to the host macrophage. Using 16PS linked to a palmitate chain, which enabled it to complex with low density lipoproteins, improved the leishmanicidal efficiency on intracellular amastigotes, probably due to increased endocytosis. Phosphorothioate oligonucleotides complementary to the intron part of the mini-exon pre-RNA were also effective, suggesting that antisense oligomers could prevent trans-splicing in these parasites.
Authors:
C Ramazeilles; R K Mishra; S Moreau; E Pascolo; J J Toulmé
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  91     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1994 Aug 
Date Detail:
Created Date:  1994-09-14     Completed Date:  1994-09-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7859-63     Citation Subset:  IM    
Affiliation:
Laboratoire de Biophysique Moléculaire Institut National de la Santé et de la Recherche Médicale Unité 386, Université de Bordeaux II, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antiprotozoal Agents / administration & dosage,  toxicity*
Base Sequence
Cells, Cultured
Drug Carriers
Exons
Introns
Leishmania mexicana / drug effects*,  genetics,  growth & development
Lipoproteins, LDL
Macrophages, Peritoneal / drug effects,  parasitology
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Oligonucleotides, Antisense / administration & dosage,  toxicity*
Protein Biosynthesis / drug effects
RNA Splicing / drug effects
RNA, Messenger / genetics
Thionucleotides / toxicity*
Chemical
Reg. No./Substance:
0/Antiprotozoal Agents; 0/Drug Carriers; 0/Lipoproteins, LDL; 0/Oligonucleotides, Antisense; 0/RNA, Messenger; 0/Thionucleotides
Comments/Corrections

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