The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Therapeutic siRNA: State-of-the-Art and Future Perspectives
Open accessAbstract
The highly specific induction of RNA interference-mediated gene knockdown, based on the direct application of small interfering RNAs (siRNAs), opens novel avenues towards innovative therapies. Two decades after the discovery of the RNA interference mechanism, the first siRNA drugs received approval for clinical use by the US Food and Drug Administration and the European Medicines Agency between 2018 and 2022. These are mainly based on an siRNA conjugation with a targeting moiety for liver hepatocytes, N-acetylgalactosamine, and cover the treatment of acute hepatic porphyria, transthyretin-mediated amyloidosis, hypercholesterolemia, and primary hyperoxaluria type 1. Still, the development of siRNA therapeutics faces several challenges and issues, including the definition of optimal siRNAs in terms of target, sequence, and chemical modifications, siRNA delivery to its intended site of action, and the absence of unspecific off-target effects. Further siRNA drugs are in clinical studies, based on different delivery systems and covering a wide range of different pathologies including metabolic diseases, hematology, infectious diseases, oncology, ocular diseases, and others. This article reviews the knowledge on siRNA design and chemical modification, as well as issues related to siRNA delivery that may be addressed using different delivery systems. Details on the mode of action and clinical status of the various siRNA therapeutics are provided, before giving an outlook on issues regarding the future of siRNA drugs and on their potential as one emerging standard modality in pharmacotherapy. Notably, this may also cover otherwise un-druggable diseases, the definition of non-coding RNAs as targets, and novel concepts of personalized and combination treatment regimens.
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Cites
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Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis
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Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer
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Rational siRNA design for RNA interference
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Rational design of cationic lipids for siRNA delivery
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“Other drawbacks of nanoparticles such as LNPs include that it is often necessary to administer them intravenously, making it a comparatively complex process that is unfavorable for patients.”
BackgroundInfluentialDelivery materials for siRNA therapeutics
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Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol
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Therapeutic siRNA: state of the art
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The current state and future directions of RNAi-based therapeutics
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Cited by
Harnessing RNA Interference for Cholesterol Lowering: The Bench‐to‐Bedside Story of Inclisiran
Wilkinson, M. J., Bajaj, A., Brousseau, M. E., & Taub, P. R. (2024) · Journal of the American Heart Association · doi:10.1161/jaha.123.032031 · Cited by 37
GalNac-siRNA conjugate delivery technology promotes the treatment of typical chronic liver diseases
Qin, Z.-X., Zuo, L., Zeng, Z., Ma, R., Xie, W., Zhu, X., & Zhou, X. (2025) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2025.2466767 · Cited by 32
Targeting PCSK9 With Antibodies and Gene Silencing to Reduce LDL Cholesterol
Newman, C. B., & Tobert, J. A. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac708 · Cited by 20
Metadata
- Authors
- Friedrich, M., & Aigner, A.
- Venue
- BioDrugs
- Published
- 2022-08-23
- Volume
- 36
- Issue
- 5
- Pages
- 549-571
- ISSN
- 1172-7039 (ISSN-L)
- 1173-8804
- 1179-190X
- OpenAlex
- W4292702578
- Cited by
- 396
- References
- 27
- FWCI
- 21.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
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