Safety and efficacy of RNAi therapy for transthyretin amyloidosis
Open accessAbstract
BACKGROUND: Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and the heart. A therapeutic approach mediated by RNA interference (RNAi) could reduce the production of transthyretin. METHODS: We identified a potent antitransthyretin small interfering RNA, which was encapsulated in two distinct first- and second-generation formulations of lipid nanoparticles, generating ALN-TTR01 and ALN-TTR02, respectively. Each formulation was studied in a single-dose, placebo-controlled phase 1 trial to assess safety and effect on transthyretin levels. We first evaluated ALN-TTR01 (at doses of 0.01 to 1.0 mg per kilogram of body weight) in 32 patients with transthyretin amyloidosis and then evaluated ALN-TTR02 (at doses of 0.01 to 0.5 mg per kilogram) in 17 healthy volunteers. RESULTS: Rapid, dose-dependent, and durable lowering of transthyretin levels was observed in the two trials. At a dose of 1.0 mg per kilogram, ALN-TTR01 suppressed transthyretin, with a mean reduction at day 7 of 38%, as compared with placebo (P=0.01); levels of mutant and nonmutant forms of transthyretin were lowered to a similar extent. For ALN-TTR02, the mean reductions in transthyretin levels at doses of 0.15 to 0.3 mg per kilogram ranged from 82.3 to 86.8%, with reductions of 56.6 to 67.1% at 28 days (P<0.001 for all comparisons). These reductions were shown to be RNAi-mediated. Mild-to-moderate infusion-related reactions occurred in 20.8% and 7.7% of participants receiving ALN-TTR01 and ALN-TTR02, respectively. CONCLUSIONS: ALN-TTR01 and ALN-TTR02 suppressed the production of both mutant and nonmutant forms of transthyretin, establishing proof of concept for RNAi therapy targeting messenger RNA transcribed from a disease-causing gene. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov numbers, NCT01148953 and NCT01559077.).
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The Acuitas mRNA delivery platform has been developed from technology shown previously to enable siRNA-dependent hepatic gene silencing across species in rodents, nonhuman primates and humans.
“The Acuitas mRNA delivery platform has been developed from technology shown previously to enable siRNA-dependent hepatic gene silencing across species in rodents, nonhuman primates and humans.28,43,44”
From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [44]
The Discussion (page not supplied) reports that lipid-nanoparticle siRNA delivery silenced liver-expressed genes in animals, including nonhuman primates, and that this study demonstrated RNAi-mediated gene modulation in human liver. The paper also discusses results across multiple species, but our copy does not establish that the Acuitas mRNA platform was developed from this technology. (LLM, conf=0.84)
Experimental — accuracy not yet measuredsiRNAs are large, negatively-charged, double-stranded molecules that require formulation or chemical conjugation for delivery to tissues, especially the CNS.
“siRNAs are large, negatively-charged, double-stranded molecules that require formulation6 or chemical conjugation7–10 for delivery to tissues (especially CNS).”
From A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system (2019) · cites this paper as [6]
Citation 6 is attached to formulation. The paper describes lipid-nanoparticle formulations that deliver siRNAs to hepatocytes, supporting that part of the sentence. But it says these systemically administered formulations do not penetrate the CNS, so it does not support the CNS qualifier. The provided copy gives no page number for the relevant passage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe success of the first approved siRNA-LNP therapeutic and mRNA COVID-19 vaccines originates only from their delivery using ionizable lipid-containing LNPs.
“Based on the potential toxicity of liposomes in clinical application,25,26 the success of the first approved small interfering RNA-lipid nanoparticle (LNP) therapeutic27 and mRNA COVID-19 vaccines originates only from their delivery using ionizable lipid-containing LNPs,28, 29, 30”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [29]
The combined functionality of Patisiran's RNAi technique and LNPs enables robust reduction in expression of the hATTR disease-linked gene, providing a therapeutic treatment for the genetic disease.
“The combined functionality of Patisiran’s RNAi technique coupled with the use of LNPs as a delivery vehicle enables a robust reduction in the expression of the hATTR disease-linked gene, ultimately providing a therapeutic treatment for the genetic disease.[56, 57]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [57]
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Cites
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C. (1998) · Nature · doi:10.1038/35888 · Cited by 15,429 · see citing works
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456 · see citing works
Rowinsky, E. K., & Donehower, R. C. (1995) · New England Journal of Medicine · doi:10.1056/nejm199504133321507 · Cited by 1,924 · see citing works
RNAi-mediated gene silencing in non-human primates
Zimmermann, T. S., Lee, A. C. H., Akinc, A., Bramlage, B., Bumcrot, D., Fedoruk, M. N., Harborth, J., Heyes, J. A., Jeffs, L. B., John, M., et al. (2006) · Nature · doi:10.1038/nature04688 · Cited by 1,357 · see citing works
Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo
Jayaraman, M., Ansell, S. M., Mui, B. L., Tam, Y. K., Chen, J., Du, X., Butler, D., Eltepu, L., Matsuda, S., Narayanannair, J. K., et al. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201203263 · Cited by 1,267 · see citing works
Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms
Akinc, A., Querbes, W., De, S., Qin, J., Frank-Kamenetsky, M., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Cantley, W. L., Dorkin, J. R., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.85 · Cited by 1,261 · see citing works
RNAi therapeutics: a potential new class of pharmaceutical drugs
Bumcrot, D. A., Manoharan, M., Koteliansky, V., & Sah, D. W. Y. (2006) · Nature Chemical Biology · doi:10.1038/nchembio839 · Cited by 1,086 · see citing works
Self-citationNatural History and Outcome in Systemic AA Amyloidosis
Lachmann, H. J., Goodman, H. J. B., Gilbertson, J. A., Gallimore, J. R., Sabin, C. A., Gillmore, J. D., & Hawkins, P. N. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa070265 · Cited by 1,025 · see citing works
Self-citationTafamidis for transthyretin familial amyloid polyneuropathy
Coelho, T., Maia, L. F., SILVA, A. C. F. D., Waddington‐Cruz, M., Planté‐Bordeneuve, V., Lozeron, P., Suhr, O. B., Campistol, J. M., Conceição, I. M., Schmidt, H., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e3182661eb1 · Cited by 812 · see citing works
Self-citationFamilial amyloid polyneuropathy
Planté‐Bordeneuve, V., & Saïd, G. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70246-0 · Cited by 645 · see citing works
Frank-Kamenetsky, M. D., Grefhorst, A., Anderson, N. N., Racie, T., Bramlage, B., Akinc, A., Butler, D., Charissé, K., Dorkin, J. R., Fan, Y., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805434105 · Cited by 635 · see citing works
Self-citationBreathnach, S. M. (1988) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(88)70001-8 · Cited by 621 · see citing works
Fate and behavior of liposomes in vivo: a review of controlling factors.
Senior, J. H. (1987) · PubMed · Cited by 592 · see citing works
Chanan-Khan, A., Szebeni, J., Savay, S., Liebes, L., Rafique, N. M., Alving, C. R., & Muggia, F. M. (2003) · Annals of Oncology · doi:10.1093/annonc/mdg374 · Cited by 479 · see citing works
Lachmann, H. J., Gallimore, J. R., Gillmore, J. D., Carr-Smith, H. D., Bradwell, A. R., Pepys, M. B., & Hawkins, P. N. (2003) · British Journal of Haematology · doi:10.1046/j.1365-2141.2003.04433.x · Cited by 431 · see citing works
Self-citationSzebeni, J., Muggia, F. M., Gabizón, A., & Barenholz, Y. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.06.017 · Cited by 424 · see citing works
Holmgren, G., Steen, L., Ekstedt, J., Groth, C., Ericzon, B. ‐., Eriksson, S., Andersen, O., Karlberg, I. H., Nordén, G., Nakazato, M., et al. (1991) · Clinical Genetics · doi:10.1111/j.1399-0004.1991.tb03085.x · Cited by 395 · see citing works
Self-citationTransthyretin-related amyloidoses and the heart: a clinical overview
Rapezzi, C., Quarta, C. C., Riva, L., et al. (2010) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2010.67 · Cited by 353 · see citing works
Episkopou, V, Maeda, S., Nishiguchi, S., Shimada, K., Gaitanaris, G. A., Gottesman, M. E., & Robertson, E. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.6.2375 · Cited by 325 · see citing works
A status report on RNAi therapeutics
Vaishnaw, A. K., Gollob, J., Gamba‐Vitalo, C., Hutabarat, R. M., Sah, D. W. Y., Meyers, R. E., de Fougerolles, T., & Maraganore, J. M. (2010) · Silence · doi:10.1186/1758-907x-1-14 · Cited by 297 · see citing works
Self-citationHuang, S. K., Mayhew, E. G., Gilani, S., Lasiç, D. D., Martin, F. J., & Papahadjopoulos, D. (1992) · PubMed · Cited by 274 · see citing works
Herlenius, G., Wilczek, H., Larsson, M., & Ericzon, B. (2004) · Transplantation · doi:10.1097/01.tp.0000092307.98347.cb · Cited by 274 · see citing works
Yazaki, M., Tokuda, T., Nakamura, A., Higashikata, T., Koyama, J., Higuchi, K., Harihara, Y., Baba, S., Kametani, F., & Ikeda, S. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3203 · Cited by 168 · see citing works
Progression of transthyretin amyloid neuropathy after liver transplantation
Liepnieks, J. J., Zhang, L. Q., & Benson, M. D. (2010) · Neurology · doi:10.1212/wnl.0b013e3181ea15d4 · Cited by 158 · see citing works
Forty years of experience with type I amyloid neuropathy. Review of 483 cases
Coutinho, P., da Silva, A. L., Lopes, J. M., Resende, P.-E. A., Silva, A. M. D., Resende, L. A. L., Silva, A. M.-D., Filho, J. D. L., & Barbosa, A. (1980) · Cited by 149 · see citing works
Self-citationCardiac transthyretin amyloidosis
Dungu, J. N., Anderson, L. J., Whelan, C. J., & Hawkins, P. N. (2012) · Heart · doi:10.1136/heartjnl-2012-301924 · Cited by 140 · see citing works
Self-citationPathogenesis of and Therapeutic Strategies to Ameliorate the Transthyretin Amyloidoses
Sekijima, Y., Kelly, J. W., & Ikeda, S. (2008) · Current Pharmaceutical Design · doi:10.2174/138161208786404155 · Cited by 136 · see citing works
Biochemical Basis for Depressed Serum Retinol Levels in Transthyretin-deficient Mice
van Bennekum, A. M., Wei, S., Gamble, M. V., Vogel, S., Piantedosi, R., Gottesman, M., Episkopou, V., & Blaner, W. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008091200 · Cited by 136 · see citing works
Liver transplantation for familial amyloidotic polyneuropathy: Impact on Swedish patients' survival
Okamoto, S., Wixner, J., Obayashi, K., Ando, Y., Ericzon, B., Friman, S., Uchino, M., & Suhr, O. B. (2009) · Liver Transplantation · doi:10.1002/lt.21817 · Cited by 131 · see citing works
Self-citationBiesalski, H. K., Frank, J., Beck, S. C., Heinrich, F., Illek, B., Reifen, R., Gollnick, H., Seeliger, M. W., Wissinger, B., & Zrenner, E. (1999) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.5.931 · Cited by 124 · see citing works
Yazaki, M., Mitsuhashi, S., Tokuda, T., et al. (2006) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2006.01585.x · Cited by 119 · see citing works
Liver transplantation in transthyretin-related familial amyloid polyneuropathy
Stangou, A. J., & Hawkins, P. N. (2004) · Current Opinion in Neurology · doi:10.1097/00019052-200410000-00012 · Cited by 110 · see citing works
Self-citationBuxbaum, J. N., Alexander, A. A., Koziol, J. A., Tagoe, C. E., Fox, E. R., & Kitzman, D. W. (2010) · American Heart Journal · doi:10.1016/j.ahj.2010.02.006 · Cited by 107 · see citing works
Ong, D. E., Davis, J. T., O'Day, W. T., & Bok, D. (1994) · Biochemistry · doi:10.1021/bi00173a029 · Cited by 103 · see citing works
Risk of transmission of systemic transthyretin amyloidosis after domino liver transplantation
Lladó, L., Baliellas, C., Casasnovas, C., Ferrer, I., Fabregat, J., Ramos, E., Castellote, J., Torras, J., Xiol, X., & Rafecas, A. (2010) · Liver Transplantation · doi:10.1002/lt.22174 · Cited by 103 · see citing works
Ando, Y., Terazaki, H., Nakamura, M., et al. (2004) · Transplantation · doi:10.1097/01.tp.0000111516.60013.e6 · Cited by 98 · see citing works
[Cardiac Transthyretin Amyloidosis].
Manganiello, C. F. (2020) · PubMed · Cited by 96 · see citing works
Heart complications in familial transthyretin amyloidosis: impact of age and gender
Hörnsten, R., Pennlert, J., Wiklund, U., et al. (2010) · Amyloid · doi:10.3109/13506129.2010.483114 · Cited by 88 · see citing works
Transthyretin Cardiac Amyloidoses in Older North Americans
Dharmarajan, K., & Maurer, M. S. (2012) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2011.03868.x · Cited by 79 · see citing works
Familial amyloid polyneuropathy: new developments in genetics and treatment.
Coelho, T. (1996) · PubMed · Cited by 79 · see citing works
Self-citationFamilial amyloid polyneuropathy
Coelho, T. (1996) · Current Opinion in Neurology · doi:10.1097/00019052-199610000-00007 · Cited by 73 · see citing works
Self-citationAboard transthyretin: From transport to cleavage
Liz, M. A., Mar, F. M., Franquinho, F., & Sousa, M. M. (2010) · IUBMB Life · doi:10.1002/iub.340 · Cited by 66 · see citing works
Vitamin A: Overlapping delivery pathways to tissues from the circulation
Paik, J., Vogel, S., Quadro, L., Piantedosi, R., Gottesman, M., Lai, K., Hamberger, L., de Morais Vieira, M., & Blaner, W. S. (2004) · The Journal of Nutrition · doi:10.1093/jn/134.1.276s · Cited by 62 · see citing works
Transthyretin Deposition in Familial Amyloidotic Polyneuropathy
Saraiva, M. J., Magalhães, J., Ferreira, N., et al. (2012) · Current Medicinal Chemistry · doi:10.2174/092986712800269236 · Cited by 61 · see citing works
Contribution of wild‐type transthyretin to hereditary peripheral nerve amyloid
Yazaki, M., Liepnieks, J. J., Kincaid, J. C., et al. (2003) · Muscle & Nerve · doi:10.1002/mus.10452 · Cited by 53 · see citing works
Diagnosis and Therapeutic Approaches to Transthyretin Amyloidosis
Ando, Y., & Ueda, M. (2012) · Current Medicinal Chemistry · doi:10.2174/092986712800269317 · Cited by 49 · see citing works
Skinner, M., Connors, L. H., Rubinow, A., et al. (1985) · The American Journal of the Medical Sciences · doi:10.1097/00000441-198501000-00003 · Cited by 38 · see citing works
Variant transthyretin in cerebrospinal fluid in familial amyloidotic polyneuropathy
Nakazato, M., Kangawa, K., Kurihara, T., et al. (1987) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(87)90265-6 · Cited by 20 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- Ando Y, Ueda M. Diagnosis and thera- peutic approaches to transthyretin amy- loidosis. Curr Med Chem 2012;19:2312- 23.
- Dungu JN, Anderson LJ, Whelan CJ, Hawkins PN. Cardiac transthyretin amy- loidosis. Heart 2012;98:1546-54.
- Stangou AJ, Hawkins PN. Liver trans- plantation in transthyretin-related famil- ial amyloid polyneuropathy. Curr Opin Neurol 2004;17:615-20.
- Rowinsky EK, Donehower RC. Pacli- taxel (Taxol). N Engl J Med 1995;332: 1004-14. [Erratum, N Engl J Med 1995; 333:75.]
Cited by
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Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis
Adams, D., Gonzalez-Duarte, A., O’Riordan, W. D., Yang, C.-C., Ueda, M., Kristen, A. V., Tournev, I., Schmidt, H. H., Coelho, T., Berk, J. L., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1716153 · Cited by 3,047 · see citing works
Self-citationmRNA-based therapeutics--developing a new class of drugs
Sahin, U., Karikó, K., & Türeci, Ö. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4278 · Cited by 2,474 · see citing works
The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs
Akinc, A., Maier, M. A., Manoharan, M., Fitzgerald, K., Jayaraman, M., Barros, S., Ansell, S., Du, X., Hope, M. J., Madden, T. D., et al. (2019) · Nature Nanotechnology · doi:10.1038/s41565-019-0591-y · Cited by 1,636 · see citing works
Self-citationZuris, J. A., Thompson, D. B., Shu, Y., Guilinger, J. P., Bessen, J. L., Hu, J. H., Maeder, M. L., Joung, J. K., Chen, Z.-Y., & Liu, D. R. (2015) · Nature Biotechnology · doi:10.1038/nbt.3081 · Cited by 1,460 · see citing works
Lipid Nanoparticle Systems for Enabling Gene Therapies
Cullis, P. R., & Hope, M. J. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.03.013 · Cited by 1,208 · see citing works
Nair, J. K., Willoughby, J. L. S., Chan, A., Charisse, K., Alam, M. R., Wang, Q., Hoekstra, M., Kandasamy, P., Kel’in, A. V., Milstein, S., et al. (2014) · Journal of the American Chemical Society · doi:10.1021/ja505986a · Cited by 1,141 · see citing works
Self-citationsiRNA versus miRNA as therapeutics for gene silencing
Lam, J. K. W., Chow, M. Y. T., Zhang, Y., & Leung, S. W. S. (2015) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2015.23 · Cited by 1,081 · see citing works
Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines
Hassett, K. J., Benenato, K. E., Jacquinet, E., Lee, A., Woods, A., Yuzhakov, O., Himansu, S., Deterling, J., Geilich, B. M., Ketova, T., et al. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.01.013 · Cited by 927 · see citing works
Modified mRNA vaccines protect against zika virus infection
Richner, J. M., Himansu, S., Dowd, K. A., Butler, S. L., Salazar, V., Fox, J. M., Julander, J. G., Tang, W. W., Shresta, S., Pierson, T. C., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.017 · Cited by 909 · see citing works
Crooke, S. T., Witztum, J. L., Bennett, C. F., & Baker, B. F. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.004 · Cited by 841 · see citing works
Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia
Raal, F. J., Kallend, D., Ray, K. K., Turner, T., Koenig, W., Wright, R. S., Wijngaard, P. L. J., Curcio, D., Jaros, M. J., Leiter, L. A., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1913805 · Cited by 818 · see citing works
Sabnis, S., Kumarasinghe, E. S., Salerno, T., Mihai, C., Ketova, T., Senn, J. J., Lynn, A., Bulychev, A., McFadyen, I., Chan, J., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.03.010 · Cited by 820 · see citing works
A highly durable RNAi therapeutic inhibitor of PCSK9
Fitzgerald, K., White, S., Borodovsky, A., Bettencourt, B. R., Strahs, A., Clausen, V., Wijngaard, P., Horton, J. D., Taubel, J., Brooks, A., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1609243 · Cited by 768 · see citing works
Self-citationVisualizing lipid-formulated siRNA release from endosomes and target gene knockdown
Wittrup, A., Ai, A., Liu, X., Hamar, P., Trifonova, R., Charisse, K., Manoharan, M., Kirchhausen, T., & Lieberman, J. (2015) · Nature Biotechnology · doi:10.1038/nbt.3298 · Cited by 693 · see citing works
Advances in the delivery of RNA therapeutics: from concept to clinical reality
Kaczmarek, J. C., Kowalski, P. S., & Anderson, D. G. (2017) · Genome Medicine · doi:10.1186/s13073-017-0450-0 · Cited by 656 · see citing works
Bahl, K., Senn, J. J., Yuzhakov, O., Bulychev, A., Brito, L. A., Hassett, K. J., Laska, M. E., Smith, M., Almarsson, Ö., Thompson, J., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.03.035 · Cited by 642 · see citing works
Maier, M. A., Jayaraman, M., Matsuda, S., Liu, J., Barros, S., Querbes, W., Tam, Y. K., Ansell, S. M., Kumar, V., Qin, J., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2013.124 · Cited by 625 · see citing works
Self-citationDelivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications
Liu, C., Zhang, L., Liu, H., & Cheng, K. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.09.012 · Cited by 607 · see citing works
Lipid nanoparticles enabling gene therapies: from concepts to clinical utility
Kulkarni, J. A., Cullis, P. R., & van der Meel, R. (2018) · Nucleic Acid Therapeutics · doi:10.1089/nat.2018.0721 · Cited by 592 · see citing works
Thess, A., Grund, S., Mui, B. L., Hope, M. J., Baumhof, P., Fotin-Mleczek, M., & Schlake, T. (2015) · Molecular Therapy · doi:10.1038/mt.2015.103 · Cited by 513 · see citing works
Integrating Artificial Intelligence and Nanotechnology for Precision Cancer Medicine
Adir, O., Poley, M., Chen, G., Froim, S., Krinsky, N., Shklover, J., Shainsky‐Roitman, J., Lammers, T., & Schroeder, A. (2020) · Advanced Materials · doi:10.1002/adma.201901989 · Cited by 496 · see citing works
Diagnosis, Prognosis, and Therapy of Transthyretin Amyloidosis
Gertz, M. A., Benson, M. D., Dyck, P. J., Grogan, M., Coelho, T., Cruz, M., Berk, J. L., Plante-Bordeneuve, V., Schmidt, H. H. J., & Merlini, G. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.09.075 · Cited by 475 · see citing works
Self-citationExosome-mediated delivery of hydrophobically modified siRNA for huntingtin mRNA silencing
Didiot, M.-C., Hall, L. M., Coles, A. H., Haraszti, R. A., Godinho, B. M., Chase, K., Sapp, E., Ly, S., Alterman, J. F., Hassler, M. R., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.126 · Cited by 483 · see citing works
Solomon, S. D., Adams, D., Kristen, A., Grogan, M., González-Duarte, A., Maurer, M. S., Merlini, G., Damy, T., Slama, M. S., Brannagan, T. H., et al. (2019) · Circulation · doi:10.1161/circulationaha.118.035831 · Cited by 462 · see citing works
Self-citationLiang, F., Lindgren, G., Lin, A., Thompson, E. A., Ols, S., Röhss, J., John, S., Hassett, K., Yuzhakov, O., Bahl, K., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.08.006 · Cited by 395 · see citing works
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Advanced siRNA Designs Further Improve In Vivo Performance of GalNAc-siRNA Conjugates
Foster, D. J., Brown, C. R., Shaikh, S., Trapp, C., Schlegel, M. K., Qian, K., Sehgal, A., Rajeev, K. G., Jadhav, V., Manoharan, M., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2017.12.021 · Cited by 325 · see citing works
Self-citationSuhr, O. B., Coelho, T., Buades, J., Pouget, J., Conceicao, I., Berk, J., Schmidt, H., Waddington-Cruz, M., Campistol, J. M., Bettencourt, B. R., et al. (2015) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-015-0326-6 · Cited by 321 · see citing works
Self-citationSago, C. D., Lokugamage, M. P., Paunovska, K., Vanover, D. A., Monaco, C. M., Shah, N. N., Gamboa Castro, M., Anderson, S. E., Rudoltz, T. G., Lando, G. N., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811276115 · Cited by 313 · see citing works
COVID-19 mRNA vaccines: Platforms and current developments
Szabó, G. T., Mahiny, A. J., & Vlatkovic, I. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.02.016 · Cited by 308 · see citing works
Going beyond the liver: progress and challenges of targeted delivery of siRNA therapeutics
Lorenzer, C., Dirin, M., Winkler, A.-M., Baumann, V., & Winkler, J. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.02.003 · Cited by 284 · see citing works
Jung, H. N., Lee, S.-Y., Lee, S., Youn, H., & Im, H.-J. (2022) · Theranostics · doi:10.7150/thno.77259 · Cited by 282 · see citing works
Patisiran, an RNAi Therapeutic for the Treatment of Hereditary Transthyretin-Mediated Amyloidosis
Kristen, A. V., Ajroud-Driss, S., Conceição, I., Gorevic, P., Kyriakides, T., & Obici, L. (2019) · Neurodegenerative Disease Management · doi:10.2217/nmt-2018-0033 · Cited by 268 · see citing works
Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines
Lutz, J., Lazzaro, S., Habbeddine, M., Schmidt, K. E., Baumhof, P., Mui, B. L., Tam, Y. K., Madden, T. D., Hope, M. J., Heidenreich, R., et al. (2017) · npj Vaccines · doi:10.1038/s41541-017-0032-6 · Cited by 257 · see citing works
An RNA toolbox for cancer immunotherapy
Pastor, F., Berraondo, P., Etxeberria, I., Frederick, J., Sahin, U., Gilboa, E., & Melero, I. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.132 · Cited by 229 · see citing works
Alterman, J. F., Godinho, B. M. D. C., Hassler, M. R., Ferguson, C. M., Echeverria, D., Sapp, E., Haraszti, R. A., Coles, A. H., Conroy, F., Miller, R., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0205-0 · Cited by 227 · see citing works
Cheng, Q., Wei, T., Jia, Y., Farbiak, L., Zhou, K., Zhang, S., Wei, Y., Zhu, H., & Siegwart, D. J. (2018) · Advanced Materials · doi:10.1002/adma.201805308 · Cited by 221 · see citing works
Sedic, M., Senn, J. J., Lynn, A., Laska, M., Smith, M., Platz, S. J., Bolen, J., Hoge, S., Bulychev, A., Jacquinet, E., et al. (2018) · Veterinary Pathology · doi:10.1177/0300985817738095 · Cited by 195 · see citing works
Macrophages retain hematopoietic stem cells in the spleen via VCAM-1
Dutta, P., Hoyer, F. F., Grigoryeva, L. S., Sager, H. B., Leuschner, F., Courties, G., Borodovsky, A., Novobrantseva, T., Ruda, V. M., Fitzgerald, K., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20141642 · Cited by 180 · see citing works
Self-citationMeyer, M., Huang, E., Yuzhakov, O., Ramanathan, P., Ciaramella, G., & Bukreyev, A. (2018) · The Journal of Infectious Diseases · doi:10.1093/infdis/jix592 · Cited by 178 · see citing works
Adams, D., Polydefkis, M., González-Duarte, A., Wixner, J., Kristen, A. V., Schmidt, H. H., Berk, J. L., Losada López, I. A., Dispenzieri, A., Quan, D., et al. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30368-9 · Cited by 158 · see citing works
Self-citationLipid nanoparticles for targeted siRNA delivery - going from bench to bedside
Zatsepin (2016) · International Journal of Nanomedicine · doi:10.2147/ijn.s106625 · Cited by 162 · see citing works
Paunovska, K., Gil, C. J., Lokugamage, M. P., Sago, C. D., Sato, M., Lando, G. N., Gamboa Castro, M., Bryksin, A. V., & Dahlman, J. E. (2018) · ACS Nano · doi:10.1021/acsnano.8b03640 · Cited by 160 · see citing works
Lipid nanoparticles for short interfering RNA delivery
Leung, A. K. K., Tam, Y. Y. C., & Cullis, P. R. (2014) · Advances in genetics · doi:10.1016/b978-0-12-800148-6.00004-3 · Cited by 158 · see citing works
Lindgren, G., Ols, S., Liang, F., Thompson, E. A., Lin, A., Hellgren, F., Bahl, K., John, S., Yuzhakov, O., Hassett, K. J., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01539 · Cited by 132 · see citing works
Chan, A., Liebow, A., Yasuda, M., Gan, L., Racie, T., Maier, M., Kuchimanchi, S., Foster, D., Milstein, S., Charisse, K., et al. (2015) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2015.36 · Cited by 128 · see citing works
Self-citationPreclinical evaluation of RNAi as a treatment for transthyretin-mediated amyloidosis
Butler, J. S., Chan, A., Costelha, S., Fishman, S., Willoughby, J. L. S., Borland, T. D., Milstein, S., Foster, D. J., Gonçalves, P., Chen, Q., et al. (2016) · Amyloid · doi:10.3109/13506129.2016.1160882 · Cited by 113 · see citing works
Self-citationShi, H., Wang, X., Li, F., Gerlach, B. D., Yurdagul, A., Moore, M. P., Zeldin, S., Zhang, H., Cai, B., Zheng, Z., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abp8309 · Cited by 85 · see citing works
RNA delivery biomaterials for the treatment of genetic and rare diseases
Zhao, W., Hou, X., Vick, O. G., & Dong, Y. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119291 · Cited by 82 · see citing works
siRNA-lipid nanoparticles with long-term storage stability facilitate potent gene-silencing in vivo
Suzuki, Y., Hyodo, K., Tanaka, Y., & Ishihara, H. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.10.024 · Cited by 71 · see citing works
Intraventricular Delivery of siRNA Nanoparticles to the Central Nervous System
Shyam, R., Ren, Y., Lee, J., Braunstein, K. E., Mao, H.-Q., & Wong, P. C. (2015) · Molecular Therapy - Nucleic Acids · doi:10.1038/mtna.2015.15 · Cited by 58 · see citing works
Interphotoreceptor Retinoid-Binding Protein (IRBP) in Retinal Health and Disease
Zeng, S., Zhang, T., Madigan, M. C., Fernando, N., Aggio-Bruce, R., Zhou, F., Pierce, M., Chen, Y., Huang, L., Natoli, R., et al. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.577935 · Cited by 37 · see citing works
“Several other studies have also demonstrated the successful application of nanoparticles in the liver with approval by the US Food and Drug Administration (FDA) (Coelho et al., 2013; Rizk and Tuzmen, 2017).”
BackgroundEbenezer, O., Comoglio, P., Wong, G. K.-S., & Tuszynski, J. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24044019 · Cited by 39 · see citing works
Nucleic acid therapies for cystic fibrosis
Sasaki, S., & Guo, S. (2018) · Nucleic Acid Therapeutics · doi:10.1089/nat.2017.0696 · Cited by 24 · see citing works
Pandey, M., Ojha, D., Bansal, S., Rode, A. B., & Chawla, G. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.101003 · Cited by 23 · see citing works
Enhancing siRNA delivery by employing lipid nanoparticles
Hope, M. J. (2014) · Therapeutic Delivery · doi:10.4155/tde.14.37 · Cited by 22 · see citing works
APOE polymorphism in ATTR amyloidosis patients treated with lipid nanoparticle siRNA
Niemietz, C., Nadzemova, O., Zibert, A., & Schmidt, H. H.-J. (2020) · Amyloid · doi:10.1080/13506129.2019.1681392 · Cited by 22 · see citing works
Tam, Y. K., Madden, T. D., & Hope, M. J. (2016) · Journal of Drug Targeting · doi:10.1080/1061186x.2016.1221955 · Cited by 20 · see citing works
- Authors
- Coelho, T., Adams, D., Silva, A., Lozeron, P., Hawkins, P. N., Mant, T., Perez, J., Chiesa, J., Warrington, S., Tranter, E., Munisamy, M., Falzone, R., Harrop, J., Cehelsky, J., Bettencourt, B. R., Geissler, M., Butler, J. S., Sehgal, A., Meyers, R. E., Chen, Q., Borland, T., Hutabarat, R. M., Clausen, V. A., Alvarez, R., Fitzgerald, K., Gamba-Vitalo, C., Nochur, S. V., Vaishnaw, A. K., Sah, D. W. Y., Gollob, J. A., & Suhr, O. B.
- Affiliations
- Hospital de Santo António (PT)
- Université Paris-Sud (FR)
- Alnylam Pharmaceuticals (United States) (US)
- The Royal Free Hospital (GB)
- IQVIA (United Kingdom) (GB)
- Hammersmith Medicines Research (GB)
- Umeå University (SE)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2013-08-29
- Volume
- 369
- Issue
- 9
- Pages
- 819-829
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2080718344
- Cited by
- 971
- References
- 48
- Citations by year
- 2026: 31 · 2025: 50 · 2024: 64 · 2023: 53 · 2022: 62 · 2021: 58 · 2020: 75 · 2019: 91 · 2018: 66 · 2017: 98 · 2016: 99 · 2015: 122 · 2014: 84 · 2013: 18
- FWCI
- 48.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Alnylam Pharmaceuticals
- National Institute for Health and Care Research
- King's College London
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- transthyretin amyloidosis, RNA interference, siRNA, lipid nanoparticles, infusion reactions, treatment efficacy and safety, gene silencing, amyloidosis treatment, healthy volunteers
- MeSH terms
- Adolescent, Adult, Animals, Dose-Response Relationship, Drug, Female, Humans, Liposomes, Macaca fascicularis, Male, Prealbumin, Amyloid Neuropathies, Familial, RNA, Small Interfering, Nanocapsules, Young Adult
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