Therapeutic RNA-silencing oligonucleotides in metabolic diseases
Abstract
Recent years have seen unprecedented activity in the development of RNA-silencing oligonucleotide therapeutics for metabolic diseases. Improved oligonucleotide design and optimization of synthetic nucleic acid chemistry, in combination with the development of highly selective and efficient conjugate delivery technology platforms, have established and validated oligonucleotides as a new class of drugs. To date, there are five marketed oligonucleotide therapies, with many more in clinical studies, for both rare and common liver-driven metabolic diseases. Here, we provide an overview of recent developments in the field of oligonucleotide therapeutics in metabolism, review past and current clinical trials, and discuss ongoing challenges and possible future developments.
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The most common adverse event was injection-site reactions affecting 5-17% of patients across studies, but these were mild to moderate and short-lived with minimal treatment discontinuation.
“The most common adverse event was injection-site reactions affecting 5–17% of patients in different studies but these reactions were mild to moderate and short-lived with minimal need to stop treatment [15, 81].”
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References 322 · Cited by 58
- Authors
- Goga, A., & Stoffel, M.
- Affiliations
- ETH Zurich (CH)
- University of Zurich (CH)
- Corresponding author
- Stoffel, Markus
- ORCID
- Stoffel, Markus
- Venue
- Nature Reviews Drug Discovery
- Published
- 2022-02-24
- Volume
- 21
- Issue
- 6
- Pages
- 417-439
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W4213424500
- Cited by
- 58
- References
- 322
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 15 · 2023: 13 · 2022: 4
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- metabolic disorders, liver disease, oligonucleotide therapeutics, oligonucleotide design, nucleic acid chemistry, drug delivery systems, clinical trials, rare diseases
- MeSH terms
- Humans, Metabolic Diseases, Oligonucleotides, RNA, Oligonucleotides, Antisense, RNA Interference
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