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Cellular uptake and intracellular trafficking of oligonucleotides: implications for oligonucleotide pharmacology

R L Juliano1, Xin Ming, Kyle Carver

  • 1Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina , Chapel Hill, North Carolina.

Nucleic Acid Therapeutics
|January 4, 2014
PubMed

Insights

Efficiently delivering therapeutic oligonucleotides to cells is challenging. This review explores strategies like ligand conjugates and nanocarriers to improve oligonucleotide uptake and intracellular trafficking for enhanced drug action.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Therapeutic oligonucleotide delivery faces significant hurdles due to inefficient cellular uptake.
  • Cellular uptake and intracellular trafficking pathways critically impact oligonucleotide pharmacological effects.
  • Understanding endocytosis and trafficking is key to optimizing oligonucleotide-based therapies.

Purpose of the Study:

  • To review current knowledge on oligonucleotide cellular uptake and intracellular trafficking.
  • To discuss strategies for targeted delivery and subcellular localization of oligonucleotides.
  • To highlight approaches for enhancing oligonucleotide therapeutic efficacy.

Main Methods:

  • Review of recent scientific literature on oligonucleotide delivery and trafficking.
  • Discussion of various targeted delivery strategies.
  • Analysis of small molecules influencing oligonucleotide effects.

Main Results:

  • Oligonucleotide delivery efficiency is a major therapeutic constraint.
  • Ligand-oligonucleotide conjugates offer a route for targeted delivery.
  • Ligand-targeted nanocarriers and small molecules show promise for enhancing delivery and effects.

Conclusions:

  • Targeted delivery and controlled intracellular trafficking are crucial for effective oligonucleotide therapeutics.
  • Advanced strategies are being developed to overcome delivery barriers.
  • Optimizing delivery pathways will unlock the full therapeutic potential of oligonucleotides.

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