Uptake, intracellular distribution, and stability of oligodeoxynucleotide phosphorothioate by Schistosoma mansoni

L F Tao1, K A Marx, W Wongwit

  • 1Center for Tropical Diseases, University of Massachusetts-Lowell 01854, USA.

Antisense Research and Development
|January 1, 1995
PubMed

Insights

Oligodeoxynucleotide phosphorothioate (PS-oligonucleotide) uptake in Schistosoma mansoni worms is concentration-dependent and primarily occurs in the cytosol and nuclei. The drug shows slow digestion and efflux, with toxicity only at high concentrations.

Area of Science:

  • Pharmacology
  • Parasitology
  • Molecular Biology

Background:

  • Antisense oligonucleotides are a promising therapeutic class.
  • Schistosoma mansoni is a parasitic flatworm causing schistosomiasis.

Purpose of the Study:

  • To investigate the in vitro pharmacokinetics of PS-oligonucleotide in Schistosoma mansoni.
  • To determine cellular distribution, stability, and toxicity of PS-oligonucleotide in this parasite model.

Main Methods:

  • 35S-labeled PS-oligonucleotide exposure to adult Schistosoma mansoni worms in vitro.
  • Cellular fractionation to determine intracellular localization.
  • Time-course studies for uptake, efflux, and stability analysis.
  • Toxicity assays at varying PS-oligonucleotide concentrations.

Main Results:

  • Intracellular accumulation was proportional to worm mass and extracellular concentration.
  • PS-oligonucleotide localized mainly in cytosol (54%) and nuclei (33%), with minimal tegumental accumulation (13%).
  • Uptake peaked at 36 hours, followed by a decrease; slow digestion and time/temperature-dependent efflux were observed.
  • Significant toxicity occurred only above 8 mg/ml (1 mM).

Conclusions:

  • PS-oligonucleotide exhibits favorable uptake and distribution characteristics in Schistosoma mansoni.
  • The drug demonstrates relative stability and a high toxicity threshold in vitro.
  • These findings support further investigation of PS-oligonucleotides as potential anti-schistosomal agents.

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