Cited by 687DNA and Nucleic Acid ChemistryRNA Interference and Gene DeliveryRNA and protein synthesis mechanisms

Phosphorothioates, Essential Components of Therapeutic Oligonucleotides

Eckstein, Fritz·2014·Nucleic Acid Therapeutics

Abstract

Phosphorothioates have found their usefulness in the general area of oligonucleotide therapeutic applications. Initially this modification was introduced into the antisense methodology because of the nuclease resistance of the phosphorothioate linkage in comparison with that of the phosphate linkage. However, as experimental data accumulated, it was detected that this chemical modification also facilitates cellular uptake and bioavailibity in vivo. Thus, today the majority of therapeutic oligonucleotides contain this modification. This review will discuss the historical development of this modification and present some of its chemical properties where they differ from those of the phosphate group. The antisense application will be discussed in the original context with cleavage of the target mRNA, but other target RNAs such as microRNAs and long noncoding RNAs will also be covered. It continues with applications where the target RNA should not be cleaved. A brief presentation of decoy oligonucleotides will be included, as well as some miscellaneous applications. Cellular uptake is a crucial step for oligonucleotides to reach their target and will be briefly reviewed. Lastly, a most surprising recent observation is the presence of phosphorothioate groups in bacterial DNA where functions still remain to be fully determined.

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Crossref · 10.1089/nat.2014.0506

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Authors
Eckstein, F.
Affiliations
Max Planck Society (DE)
Corresponding author
Eckstein, Fritz
Venue
Nucleic Acid Therapeutics
Published
2014-12
Volume
24
Issue
6
Pages
374-387
ISSN
  • 2159-3337 (ISSN-L)
  • 2159-3345
OpenAlex
W2316132657
Cited by
684
References
123
Citations by year
2026: 69 · 2025: 87 · 2024: 86 · 2023: 75 · 2022: 81 · 2021: 69 · 2020: 64 · 2019: 49 · 2018: 39 · 2017: 25 · 2016: 20 · 2015: 20
FWCI
2.04
Type
journal article
Language
en
Open access
closed
Locations
  • Nucleic Acid Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
phosphorothioate, oligonucleotide therapeutics, antisense oligonucleotides, nuclease resistance, cellular uptake, bioavailability, microRNA targeting, long non-coding RNA, decoy oligonucleotides, bacterial DNA
MeSH terms
Animals, Humans, Protein Binding, Rabbits, Transcription Factors, Oligonucleotides, Antisense, History, 20th Century, Mice, Phosphorothioate Oligonucleotides

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