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Ammonium and arsenic trioxide are potent facilitators of oligonucleotide function when delivered by gymnosis

Xiaowei Zhang1, Daniela Castanotto1, Xueli Liu2

  • 1Department of Medical Oncology and Experimental Therapeutics, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.

Nucleic Acids Research
|March 10, 2018
PubMed

Insights

Ammonium ion (NH4+) enhances oligonucleotide (ON) activity, improving therapeutic potential without increasing toxicity. This discovery offers a new strategy for enhancing ON delivery and efficacy in various cell types, including difficult-to-transfect ones.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Oligonucleotide (ON) therapeutics require high concentrations, raising concerns about off-target effects and toxicity.
  • Lowering ON concentrations reduces therapeutic efficacy due to limited cellular uptake.

Purpose of the Study:

  • To identify novel strategies for enhancing ON activity and concentration-dependent function.
  • To evaluate ammonium ion (NH4+) as a potential enhancer for ON activity.

Main Methods:

  • Investigated the effect of NH4+ on ON activity in various cell types, including attached and suspension cells.
  • Assessed NH4+ in combination with arsenic trioxide (arsenite) for synergistic effects on ON function.
  • Evaluated cellular toxicity associated with NH4+ and arsenite co-treatment.

Main Results:

  • NH4+ significantly enhanced ON activity in both the nucleus and cytoplasm across different cell lines.
  • Difficult-to-transfect cells like Jurkat T and CEM T cells showed improved ON function with NH4+.
  • NH4+ and arsenite demonstrated synergistic enhancement of ON function with no apparent increase in cellular toxicity.

Conclusions:

  • NH4+ is a potent, non-toxic enhancer of oligonucleotide activity.
  • NH4+ offers a promising strategy for improving ON-based therapies and laboratory applications.
  • Combinatorial strategies involving NH4+ could advance clinical applications of oligonucleotide therapeutics.

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