The DOI matches its Crossref record; 123 of the 123 references it cites were found in a registry or an index.
Phosphorothioates, Essential Components of Therapeutic Oligonucleotides
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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“Broad distribution of ASOs, systemically and in the CNS, has been achieved primarily using phosphorothioate (PS) backbone modifications12.”
From A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system (2019) · cites this paper as [12]
Citations
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Advances in oligonucleotide drug delivery
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Overcoming cellular barriers for RNA therapeutics
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Metadata
- Authors
- Eckstein, F.
- Affiliations
- Max Planck Society (DE)
- Corresponding author
- Eckstein, Fritz
- Venue
- Nucleic Acid Therapeutics
- Publisher
- SAGE Publications
- 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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