Mechanism of oligonucleotide uptake by cells: involvement of specific receptors?

L A Yakubov1, E A Deeva, V F Zarytova

  • 1Institute of Bioorganic Chemistry, Siberian Division of the Academy of Sciences of U.S.S.R., Novosibirsk.

Insights

Oligonucleotide derivatives enter mammalian cells via endocytosis, with higher efficiency at lower concentrations. Specific cell surface proteins likely mediate this uptake, suggesting targeted delivery potential.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Oligonucleotides and their derivatives are increasingly explored for therapeutic applications.
  • Understanding their cellular uptake mechanisms is crucial for effective drug delivery.
  • Mammalian cell interactions with these molecules require detailed investigation.

Purpose of the Study:

  • To investigate the cellular uptake mechanisms of oligonucleotides and their alkylating derivatives in mammalian cells.
  • To identify the factors influencing the efficiency of oligodeoxynucleotide uptake.
  • To explore the potential involvement of specific cellular components in oligomer binding.

Main Methods:

  • Experiments were conducted using L929 mouse fibroblast and Krebs 2 ascites carcinoma cells.
  • Cellular uptake was analyzed using varying concentrations of oligodeoxynucleotide derivatives.
  • Protein binding interactions were assessed by testing inhibition with various nucleic acids and polyanions.

Main Results:

  • Cellular uptake of oligodeoxynucleotide derivatives occurs via endocytosis.
  • Uptake efficiency is significantly higher at concentrations below 1 microM due to absorptive endocytosis.
  • Two modified proteins were detected in treated mouse fibroblasts, indicating specific interactions.
  • Binding to these proteins was inhibited by other nucleic acids but not by heparin or chondroitin sulfates.

Conclusions:

  • Oligodeoxynucleotide derivative uptake is mediated by an endocytosis mechanism, enhanced at low concentrations.
  • Specific receptor proteins on the cell surface are likely involved in the binding and internalization of oligomers.
  • These findings suggest potential for receptor-mediated drug delivery strategies using oligonucleotide derivatives.

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