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FDA approves patisiran to treat hereditary transthyretin amyloidosis
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“In 2018, Patisiran (ONPATTRO™) gained its approval by the US FDA and became the first marketed RNAi-based therapy.”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [58]
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Gene-silencing technology gets first drug approval after 20-year wait
Ledford, H. (2018) · Nature · doi:10.1038/d41586-018-05867-7 · Cited by 131
Treatment success in hereditary transthyretin amyloidosis
Fyfe, I. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0048-1 · Cited by 7
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“No other oligonucleotide-based nanomedicine has been developed and authorized at the same pace, considering, for example, the amyloidosis therapeutic Onpattro® (Patisiran) [10].”
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“Patisiran Monotherapy Rare polyneuropathy FDA approved [136]”
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“The first siRNA drug, patisiran (Table 2), was approved by the FDA in 2018 for the treatment of the polyneuropathy of hATTR amyloidosis in adults (Wood, 2018; Yu et al., 2019) over 20 years after the discovery of siRNA-controlled gene silencing.”
BackgroundInfluentialKim, M., Jeong, M., Hur, S., Cho, Y., Park, J., Jung, H. R., Seo, Y., Woo, H., Nam, K. T., Lee, K., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf4398 · Cited by 397
“These drugs target the selective degradation of mRNA to reduce the expression of diseaseassociated proteins in polyneuropathy and acute hepatic porphyria (2, 5, 9).”
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Lipid nanoparticle topology regulates endosomal escape and delivery of RNA to the cytoplasm
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“Alnylam Pharmaceuticals, Inc. (Nasdaq), the leading RNAi therapeutics company, developed this lipid complex drug to treat familial amyloid polyneuropathy (FAP) in adults (Wood, 2018).”
BackgroundGenome Editing with mRNA Encoding ZFN, TALEN, and Cas9
Zhang, H., Zhang, Y., & Yin, H. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.01.014 · Cited by 256
“An LNP-encapsulated siRNA drug named patisiran has been approved by the FDA for treating ATTR amyloidosis with polyneuropathy.(168) It is worth noting that, although CRISPR is likely used to target the same protein as RNAi therapy, CRISPR-based therapy is not a “me too” drug.”
BackgroundKheirolomoom, A., Kare, A. J., Ingham, E. S., Paulmurugan, R., Robinson, E. R., Baikoghli, M., Inayathullah, M., Seo, J. W., Wang, J., Fite, B. Z., et al. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.121339 · Cited by 171
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“In addition, the most recent approval of first-of-its-kind double-stranded siRNA patisiran by the FDA (Wood, 2018), which was shown to improve multiple clinical manifestations of hereditary transthyretin amyloidosis (Adams et al.”
BackgroundInfluentialBarbier‐Torres, L., Fortner, K. A., Iruzubieta, P., Delgado, T. C., Giddings, E. L., Chen, Y., Champagne, D., Fernández‐Ramos, D., Mestre, D., Gómez‐Santos, B., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16991-2 · Cited by 147
“The most common delivery system for siRNA to the liver has long been LNP and the fi rst LNP-formulated siRNA-based drug (Patisiran) was approved in 2018 for the treatment of hATTR (hereditary transthyretin-mediated) amyloidosis 40 .”
BackgroundMicroRNAs in Alzheimer’s Disease: Diagnostic Markers or Therapeutic Agents?
Angelucci, F., Čechová, K., Vališ, M., Kuča, K., Zhang, B., & Hort, J. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00665 · Cited by 145
“In 2018, the FDA approved the first therapy based on administration of miRNA for the treatment of rare progressive polyneuropathy caused by hereditary transthyretin-mediated (hATTR) amyloidosis (Adams et al., 2018; Wood, 2018).”
BackgroundNanomedicine-Based Approaches for mRNA Delivery
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Viral and Non-Viral Systems to Deliver Gene Therapeutics to Clinical Targets
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“A seminal study explored the use of LNP-mediated liver delivery of a siRNA targeted to treat transthyretin (TTR)-induced amyloidosis and was the first LNP-siRNA drug to achieve marketing approval in 2018 (Table 3) [115].”
BackgroundJiang, L., Lin, J., Zhao, S., Wu, J., Jin, Y., Li, Y., Wu, N., Wu, Z., Wang, Y., & Lin, M. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.703110 · Cited by 122
“…and intrathecal delivery in hereditary transthyretin amyloidosis, cytomegalovirus retinitis, and spinal muscular atrophy treatment has provided perfect examples for a safe and efficient delivery of the therapeutic construct (Group, 2002; Aartsma-Rus, 2017; Wood, 2018; Gillmore et al., 2021).”
BackgroundCurrent RNA-based Therapeutics in Clinical Trials
Zhou, L., Qin, Z., Zhu, Y., He, Z., & Xu, T. (2019) · Current Gene Therapy · doi:10.2174/1566523219666190719100526 · Cited by 118
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“1) (Wood, 2018).”
BackgroundRecent progress of polymeric nanogels for gene delivery
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RNA delivery biomaterials for the treatment of genetic and rare diseases
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“Efforts to optimize LNP systems for nucleic acid delivery led to the development of Onpattro (Patisiran) in 2018, marking the first FDA-approved treatment using small interfering RNA (siRNA), as well as the first FDA-approved LNP system [33].”
BackgroundDisruption of the NKG2A:HLA-E Immune Checkpoint Axis to Enhance NK Cell Activation against Cancer
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“This is illustrated with the approval of Onpattro, the first lipid based non-viral carrier loaded with siRNA, which is intravenously injected to treat polyneuropathy of hereditary transthyretinmediated amyloidosis [146].”
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“Recently, patisiran, a double-stranded siRNA, has been approved in the USA and EU for treating the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults [20].”
BackgroundGraphene oxide as a 2D platform for complexation and intracellular delivery of siRNA
de Lázaro, I., Vranic, S., Marson, D., Rodrigues, A. F., Buggio, M., Esteban-Arranz, A., Mazza, M., Posocco, P., & Kostarelos, K. (2019) · Nanoscale · doi:10.1039/c9nr02301a · Cited by 49
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“Several Food and Drug Administration (FDA) approved nanomedicines exist for selective cargo delivery, and recently, the first siRNA containing NP platform, Onpattro (patisiran), was granted FDA approval (Wood et al , 2018).”
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“The field currently progresses rapidly as in 2018 the FDA approved the first therapy based onmiRNA administration for the treatment of rare progressive polyneuropathy caused by hereditary transthyretinmediated amyloidosis (Adams et al., 2018; Wood, 2018).”
BackgroundTransthyretin Stabilization: An Emerging Strategy for the Treatment of Alzheimer’s Disease?
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“Food and Drug Administration for the treatment of hereditary transthyretin amyloidosis [102,103].”
BackgroundDiagnostic and Treatment Approaches Involving Transthyretin in Amyloidogenic Diseases
Park, G. Y., Jamerlan, A., Shim, K. H., & An, S. S. A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20122982 · Cited by 38
“Due to many practical difficulties of transplantation, one of the treatment options could be symptom management, which can be applied to both ATTRwt and ATTRv amyloidoses [95,96].”
BackgroundAdvances in the diagnosis and treatment of transthyretin amyloidosis with cardiac involvement
Rigopoulos, A. G., Ali, M. N. L., Abate, E., Torky, A.-R. W., Matiakis, M., Mammadov, M., Melnyk, H., Vogt, A., Vecchis, R. D., Bigalke, B., et al. (2019) · Heart Failure Reviews · doi:10.1007/s10741-019-09776-3 · Cited by 36
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“This drug works by targeting the 3ʹUTR region of transthyretin mRNA [241,242].”
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“Despite the numerous efforts over the last two decades, the first siRNA-based therapeutics, Onpattro (patisiran) by Alnylam Pharmaceuticals, was only approved by FDA in 2018 for the treatment of peripheral nerve disease, polyneuropathy, through siRNA against hereditary transthyretinmediated amyloidosis (hATTR) [80, 81…”
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“In addition, the fact that the first siRNA drug has obtained market approval most recently (52) clearly indicates the potential of siRNAs for oncogene-targeting therapies.”
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“Such studies culminated in 2018 with the success of Patisiran (ONPATTRO®), a liposomal vector developed by Alnylam Pharmaceuticals, as the first US Food and Drug Administration approved synthetic carrier of siRNA into cells (Adams et al., 2018; Hoy, 2018; Wood, 2018).”
BackgroundFopase, R., Panda, C., Rajendran, A. P., Uludağ, H., & Pandey, L. M. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1112755 · Cited by 16
“The nanoparticle-based siRNA formulation, known as Patisiran (ONPATTRO™) targets transthyretin mRNA and is used for the treatment of polyneuropathy in a hereditary form of transthyretin-mediated (hATTR) amyloidosis (Wood, 2018).”
BackgroundA Strategy Utilizing Protein–Protein Interaction Hubs for the Treatment of Cancer Diseases
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“This drug was approved by the US Food and Drug Administration in 2018 for the treatment of hereditary amyloidogenic transthyretin amyloidosis (30).”
BackgroundThe significance of bioengineered nanoplatforms against SARS-CoV-2: From detection to genome editing
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“Onpattro, a lipid NP-based siRNA drug, has paved the way for clinical translation of the lipid NP nanomedicines which contain nucleic acids for expressing or silencing the target genes [196,197].”
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“Some notable NPs for gene therapy are mRNA lipid nanoparticles (LNPs) for COVID vaccines from Pfizer and Moderna and Patirisan to treat hereditary transthyretin [12,13].”
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Borchardt, H., Schulz, A., Datta, K., Muders, M. H., & Aigner, A. M. (2019) · Scientific Reports · doi:10.1038/s41598-019-51881-8 · Cited by 10
Disease-modifying therapy for proteinopathies: Can the exception become the rule?
Bitan, G. (2019) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2019.07.010 · Cited by 10
Amirloo, B., Staroseletz, Y., Yousaf, S., Clarke, D. J., Brown, T. P., Aojula, H. S., Аркадьевна, З. М., & Bichenkova, E. V. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1273 · Cited by 9
RNA therapeutics in cardiovascular medicine
Damase, T. R., & Cooke, J. P. (2025) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000001210 · Cited by 8
Zhang, Y., Teng, Y., Xiao, W., Xu, B., Zhao, Y., Li, W., & Wu, L. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.10.009 · Cited by 9
“Patisiran is the first FDA (US Food andDrug Administration)-approved siRNA drug to treat hereditary transthyretinmediated amyloidosis (hATTR) by silencing transthyretin.(10,11) Later, givosiran is approved by the FDA to treat adults with acute hepatic porphyria by silencing aminolevulinate synthase 1 (ALAS1).”
BackgroundEmerging Contribution of PancRNAs in Cancer
Mercatelli, N., Palombo, R., & Paronetto, M. P. (2020) · Cancers · doi:10.3390/cancers12082035 · Cited by 8
Cyanuric chloride as the basis for compositionally diverse lipids
Nardo, D., Akers, C., Cheung, N. E., Isom, C. M., Spaude, J. T., Pack, D. W., & Venditto, V. J. (2021) · RSC Advances · doi:10.1039/d1ra02425f · Cited by 8
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IL-22: A key inflammatory mediator as a biomarker and potential therapeutic target for lung cancer
Xu, L., Cao, P., Wang, J., Zhang, P., Hu, S., Cheng, C., & Wang, H. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e35901 · Cited by 8
“Twenty years after the discovery of the RNA interference mechanism, the first siRNA drugs (including Patisiran, Givosiran, Lumasiran, Inclisiran, Vutrisiran) were approved for clinical use by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency from 2018 to 2022 [141,142].”
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RetractedLiu, Y., Quan, Y., Mao, Q., Xu, R., & Tai, W. (2025) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.5c00212 · Cited by 6
Zeng, Z., Zeng, X., Li, X., Feng, Y., Kan, Y., Liu, X., & Zeng, Y. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16010075 · Cited by 6
Sharma, R. K. (2023) · Current Gene Therapy · doi:10.2174/1566523223666230911120922 · Cited by 6
Which Nanobasics Should Be Taught in Medical Schools?
Sunshine, J. C., & Paller, A. S. (2019) · The AMA Journal of Ethic · doi:10.1001/amajethics.2019.337 · Cited by 6
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Nonviral vector system for cancer immunogene therapy
Nie, W., Chen, J., Wang, B., & Gao, X. (2022) · MedComm – Biomaterials and Applications · doi:10.1002/mba2.10 · Cited by 6
Real-Life Data of 2-Year Lumasiran Use in the DAILY-LUMA Cohort
Leclerc, A.-L. S., Cloarec, M., Knebelmann, B., Allard, L., Boyer, O., Cloarec, S., Dossier, C., Quintrec, M. L., Nobili, F., Stehlé, T., et al. (2024) · Kidney International Reports · doi:10.1016/j.ekir.2024.12.033 · Cited by 5
Metadata
- Authors
- Wood, H.
- Corresponding author
- Wood, Heather
- ORCID
- Wood, Heather
- Venue
- Nature Reviews Neurology
- Published
- 2018-08-29
- Volume
- 14
- Issue
- 10
- Pages
- 570-570
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- OpenAlex
- W2888899523
- Cited by
- 145
- References
- 2
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 12 · 2023: 22 · 2022: 14 · 2021: 23 · 2020: 20 · 2019: 28 · 2018: 5
- FWCI
- 6.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Internal Medicine › Amyloidosis: Diagnosis, Treatment, Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- patisiran, hereditary transthyretin amyloidosis, RNA interference therapy, prealbumin, FDA drug approval, rare genetic disorders, antisense oligonucleotides, protein misfolding
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