Receptor-Mediated Uptake of Phosphorothioate Antisense Oligonucleotides in Different Cell Types of the Liver

Colton M. Miller, Michael Tanowitz, Aaron J. Donner, Thazha P. Prakash, Eric E. Swayze, Edward N. Harris, Punit P. Seth

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Oligonucleotide therapeutics have emerged as a third distinct platform for drug discovery within the pharmaceutical industry. Five oligonucleotide-based drugs have been approved by the US FDA and over 100 oligonucleotides drugs are currently at different stages of human trials. Several of these oligonucleotide drugs are modified using the phosphorothioate (PS) backbone modification where one of the nonbridging oxygen atoms of the phosphodiester linkage is replaced with sulfur. In this review, we summarize our knowledge on receptor-mediated uptake of PS antisense oligonucleotides (ASOs) within different cell types of the liver - a privileged organ for the discovery of oligonucleotide-based therapeutics.

Original languageEnglish (US)
Pages (from-to)119-127
Number of pages9
JournalNucleic Acid Therapeutics
Volume28
Issue number3
DOIs
StatePublished - Jun 2018

Fingerprint

Phosphorothioate Oligonucleotides
Antisense Oligonucleotides
Oligonucleotides
Liver
Pharmaceutical Preparations
Drug Industry
Drug Discovery
Sulfur
Oxygen
Atoms
Therapeutics
Industry

Keywords

  • Stabilins
  • asialoglycoprotein receptor
  • hepatocytes
  • sinusoidal endothelial cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery

Cite this

Receptor-Mediated Uptake of Phosphorothioate Antisense Oligonucleotides in Different Cell Types of the Liver. / Miller, Colton M.; Tanowitz, Michael; Donner, Aaron J.; Prakash, Thazha P.; Swayze, Eric E.; Harris, Edward N.; Seth, Punit P.

In: Nucleic Acid Therapeutics, Vol. 28, No. 3, 06.2018, p. 119-127.

Research output: Contribution to journalArticle

Miller, Colton M. ; Tanowitz, Michael ; Donner, Aaron J. ; Prakash, Thazha P. ; Swayze, Eric E. ; Harris, Edward N. ; Seth, Punit P. / Receptor-Mediated Uptake of Phosphorothioate Antisense Oligonucleotides in Different Cell Types of the Liver. In: Nucleic Acid Therapeutics. 2018 ; Vol. 28, No. 3. pp. 119-127.
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