Development, opportunities, and challenges of siRNA nucleic acid drugs
Small interfering RNA (siRNA) drugs were first proposed in 1999. They have reached the market for administration to patients after more than 20 years of development. The US Food and Drug Administration has approved six siRNA drugs in recent years: patisiran, givosiran, lumasiran, vutrisiran, inclisi...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S216225312400324X |
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| author | Bowen Xiao Shaopeng Wang Yu Pan Wenjun Zhi Chensheng Gu Tao Guo Jiaqi Zhai Chenxu Li Yong Q. Chen Rong Wang |
| author_facet | Bowen Xiao Shaopeng Wang Yu Pan Wenjun Zhi Chensheng Gu Tao Guo Jiaqi Zhai Chenxu Li Yong Q. Chen Rong Wang |
| author_sort | Bowen Xiao |
| collection | DOAJ |
| description | Small interfering RNA (siRNA) drugs were first proposed in 1999. They have reached the market for administration to patients after more than 20 years of development. The US Food and Drug Administration has approved six siRNA drugs in recent years: patisiran, givosiran, lumasiran, vutrisiran, inclisiran, and nedosiran. siRNA drugs are based on the post-transcriptional gene regulation mechanism of RNA interference. These drugs have gained widespread attention for their effectiveness, low dosage, and low frequency of administration. Theoretically, siRNA drugs have great potential due to their ability to silence almost any target gene. However, drug delivery, especially the extrahepatic one, remains a major challenge. Currently, all approved drugs target the liver. The high blood flow, natural filtration function, and drug delivery methods of the liver overall ensure high efficacy and stability of the drugs themselves. This review summarizes the history of siRNA drug development and the mechanisms of action, with a focus on the drug targets, indications, and key clinical trial results to introduce the status of both marketed drugs and those currently in clinical trials. Additionally, this review provides a brief analysis of several key stages of the commercialization process of siRNA drugs. |
| format | Article |
| id | doaj-art-109b939476f547318d923cd00635ad7d |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-109b939476f547318d923cd00635ad7d2025-01-19T06:24:55ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-03-01361102437Development, opportunities, and challenges of siRNA nucleic acid drugsBowen Xiao0Shaopeng Wang1Yu Pan2Wenjun Zhi3Chensheng Gu4Tao Guo5Jiaqi Zhai6Chenxu Li7Yong Q. Chen8Rong Wang9MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaJiangnan University Medical Center, Jiangnan University, Wuxi 214122, ChinaMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China; Jiangnan University Medical Center, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China; Jiangnan University Medical Center, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; Corresponding author: Rong Wang, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.Small interfering RNA (siRNA) drugs were first proposed in 1999. They have reached the market for administration to patients after more than 20 years of development. The US Food and Drug Administration has approved six siRNA drugs in recent years: patisiran, givosiran, lumasiran, vutrisiran, inclisiran, and nedosiran. siRNA drugs are based on the post-transcriptional gene regulation mechanism of RNA interference. These drugs have gained widespread attention for their effectiveness, low dosage, and low frequency of administration. Theoretically, siRNA drugs have great potential due to their ability to silence almost any target gene. However, drug delivery, especially the extrahepatic one, remains a major challenge. Currently, all approved drugs target the liver. The high blood flow, natural filtration function, and drug delivery methods of the liver overall ensure high efficacy and stability of the drugs themselves. This review summarizes the history of siRNA drug development and the mechanisms of action, with a focus on the drug targets, indications, and key clinical trial results to introduce the status of both marketed drugs and those currently in clinical trials. Additionally, this review provides a brief analysis of several key stages of the commercialization process of siRNA drugs.http://www.sciencedirect.com/science/article/pii/S216225312400324XMT: Delivery Strategiessmall interfering RNAdrug deliverydrug targetsindicationsclinical trial |
| spellingShingle | Bowen Xiao Shaopeng Wang Yu Pan Wenjun Zhi Chensheng Gu Tao Guo Jiaqi Zhai Chenxu Li Yong Q. Chen Rong Wang Development, opportunities, and challenges of siRNA nucleic acid drugs Molecular Therapy: Nucleic Acids MT: Delivery Strategies small interfering RNA drug delivery drug targets indications clinical trial |
| title | Development, opportunities, and challenges of siRNA nucleic acid drugs |
| title_full | Development, opportunities, and challenges of siRNA nucleic acid drugs |
| title_fullStr | Development, opportunities, and challenges of siRNA nucleic acid drugs |
| title_full_unstemmed | Development, opportunities, and challenges of siRNA nucleic acid drugs |
| title_short | Development, opportunities, and challenges of siRNA nucleic acid drugs |
| title_sort | development opportunities and challenges of sirna nucleic acid drugs |
| topic | MT: Delivery Strategies small interfering RNA drug delivery drug targets indications clinical trial |
| url | http://www.sciencedirect.com/science/article/pii/S216225312400324X |
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