Systemic delivery of factor IX messenger RNA for protein replacement therapy
Open accessAbstract
Significance: Abnormal gene expression is the underlying cause for many pathological states, and restoring normalcy through overexpression or knockdown is a conceptually simple solution. Despite the advantages over DNA and viral vectors, RNA-based therapeutics have been plagued by problems of poor translatability, stability, and adverse immune reactions. Efficient in vivo delivery has also been challenging because currently available lipid nanoparticles (LNPs) can induce liver damage and elicit a strong immune response. In this study, we demonstrate the successful use of LUNAR—a safe, reproducible, and effective LNP mRNA delivery platform that can be used to treat diseases requiring protein replacement. We achieve therapeutic delivery of mRNAs in a preclinical model of hemophilia and demonstrate alleviation of disease symptoms.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
mRNA-based protein replacement therapies have been applied to haematological diseases, central nervous system disorders, skin diseases and hearing loss in preclinical studies.
“In addition, mRNA-based protein replacement therapies have been applied to haematological diseases (for example, haemophilia A232, haemophilia B91,104,233 and thrombotic thrombocytopaenic purpura234), central nervous system disorders67,152 (for example, Friedreich’s ataxia67), skin diseases235,236 (for example, elastin deficiency235) and hearing loss237 in preclinical”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [233]
The therapeutic level of FIX in plasma was maintained up to 6 days following a single i.v. administration of ATX-based LNPs complexed with 2.0 mg/kg hFIX mRNA.
“The therapeutic level of FIX in the plasma was maintained up to 6 days following a single i.v. administration of LNPs complexed with 2.0 mg/kg hFIX mRNA.[145]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [145]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Non-viral vectors for gene-based therapy
Yin, H., Kanasty, R. L., Eltoukhy, A. A., Vegas, A. J., Dorkin, J. R., & Anderson, D. G. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3763 · Cited by 3,123 · see citing works
mRNA-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
Guidelines for the management of hemophilia
Srivastava, A., Brewer, A., Mauser‐Bunschoten, E. P., Key, N. S., Kitchen, S., Llinás, A. M., Ludlam, C. A., Mahlangu, J. N., Mulder, K., Poon, M., et al. (2012) · Haemophilia · doi:10.1111/j.1365-2516.2012.02909.x · Cited by 1,949 · see citing works
Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B
Nathwani, A. C., Reiss, U. M., Tuddenham, E. G. D., Rosales, C., Chowdary, P., McIntosh, J., Della Peruta, M., Lheriteau, E., Patel, N., Raj, D., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1407309 · Cited by 1,273 · 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
AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B
Manno, C. S., Chew, A. J., Hutchison, S., Larson, P. J., Herzog, R. W., Arruda, V. R., Tai, S. J., Ragni, M. V., Thompson, A., Ozelo, M., et al. (2003) · Blood · doi:10.1182/blood-2002-10-3296 · Cited by 749 · see citing works
Expression of therapeutic proteins after delivery of chemically modified mRNA in mice
Kormann, M. S. D., Hasenpusch, G., Aneja, M. K., Nica, G., Flemmer, A. W., Herber-Jonat, S., Huppmann, M., Mays, L. E., Illenyi, M., Schams, A., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1733 · Cited by 733 · see citing works
Zangi, L., Lui, K. O., von Gise, A., Ma, Q., Ebina, W., Ptaszek, L. M., Später, D., Xu, H., Tabebordbar, M., Gorbatov, R., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2682 · Cited by 646 · see citing works
Local control of the immune response in the liver
Knolle, P. A., & Gerken, G. (2000) · Immunological Reviews · doi:10.1034/j.1600-0528.2002.017408.x · Cited by 610 · see citing works
The past and future of haemophilia: diagnosis, treatments, and its complications
Peyvandi, F., Garagiola, I., & Young, G. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01123-x · Cited by 505 · see citing works
Suhr, 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
Reversal of Diabetes Insipidus in Brattleboro Rats: Intrahypothalamic Injection of Vasopressin mRNA
Jirikowski, G. F., Sanna, P. P., Maciejewski-Lenoir, D., & Bloom, F. E. (1992) · Science · doi:10.1126/science.1546298 · Cited by 282 · see citing works
Recent progress in nanomaterials for gene delivery applications
Keleş, E., Song, Y., Du, D., Dong, W., & Lin, Y. (2016) · Biomaterials Science · doi:10.1039/c6bm00441e · Cited by 213 · see citing works
Prolonged activity of factor IX as a monomeric Fc fusion protein
Peters, R., Low, S. C., Kamphaus, G. D., Dumont, J. A., Amari, J. V., Lü, Q., Zarbis‐Papastoitsis, G., Reidy, T. J., Merricks, E. P., Nichols, T. C., et al. (2010) · Blood · doi:10.1182/blood-2009-08-239665 · Cited by 196 · see citing works
A factor IX-deficient mouse model for hemophilia B gene therapy
Wang, L., Zoppè, M., Hackeng, T. M., Griffin, J. H., Lee, K., & Verma, I. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.21.11563 · Cited by 164 · 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
Pharmacokinetics of Coagulation Factors
Bj�rkman, S., & Berntorp, E. E. (2001) · Clinical Pharmacokinetics · doi:10.2165/00003088-200140110-00003 · Cited by 159 · see citing works
Therapeutic efficacy in a hemophilia B model using a biosynthetic mRNA liver depot system
DeRosa, F., Guild, B., Karve, S., Smith, L., Love, K., Dorkin, J. R., Kauffman, K. J., Zhang, J., Yahalom, B., Anderson, D. G., et al. (2016) · Gene Therapy · doi:10.1038/gt.2016.46 · Cited by 159 · see citing works
Preclinical 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
Monahan, P. E., Sun, J., Gui, T., Hu, G., Hannah, W. B., Wichlan, D. G., Wu, Z., Grieger, J. C., Li, C., Suwanmanee, T., et al. (2015) · Human Gene Therapy · doi:10.1089/hum.2014.106 · Cited by 108 · see citing works
Petrini, P. (2001) · Haemophilia · doi:10.1046/j.1365-2516.2001.00471.x · Cited by 88 · see citing works
Gorezynski, R. M. (1992) · Immunology Letters · doi:10.1016/0165-2478(92)90095-6 · Cited by 81 · see citing works
Petrini, P. (2001) · Haemophilia · doi:10.1111/j.1365-2516.2001.00471.x · Cited by 59 · see citing works
New developments in the management of moderate-to-severe hemophilia B
Sheehan, J. P., & Nazeef, M. (2016) · Journal of Blood Medicine · doi:10.2147/jbm.s81520 · Cited by 34 · see citing works
Mancuso, M. E., Berardinelli, L., Beretta, C., Raiteri, M., Pozzoli, E., & Santagostino, E. (2009) · Haematologica · doi:10.3324/haematol.2008.001594 · Cited by 30 · see citing works
Lozier, J., Monroe, D. M., Stanfield-Oakley, S. A., et al. (1990) · Blood · doi:10.1182/blood.v75.5.1097.bloodjournal7551097 · Cited by 29 · see citing works
Brunetti‐Pierri, N., Grove, N. C., Zuo, Y., Edwards, R., Palmer, D. J., Cerullo, V., Teruya, J., & Ng, P. (2009) · Human Gene Therapy · doi:10.1089/hum.2008.084 · Cited by 23 · see citing works
Lozier, J., Monroe, D. M., Stanfield-Oakley, S. A., et al. (1990) · Blood · doi:10.1182/blood.v75.5.1097.1097 · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lipid nanoparticles for mRNA delivery
Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076 · see citing works
Cheng, Q., Wei, T., Farbiak, L., Johnson, L. T., Dilliard, S. A., & Siegwart, D. J. (2020) · Nature Nanotechnology · doi:10.1038/s41565-020-0669-6 · Cited by 2,383 · see citing works
mRNA vaccines for infectious diseases: principles, delivery and clinical translation
Chaudhary, N., Weissman, D., & Whitehead, K. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00283-5 · Cited by 1,555 · see citing works
Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery
Kowalski, P. S., Rudra, A., Miao, L., & Anderson, D. G. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.02.012 · Cited by 1,127 · see citing works
Tools for translation: non-viral materials for therapeutic mRNA delivery
Hajj, K. A., & Whitehead, K. A. (2017) · Nature Reviews Materials · doi:10.1038/natrevmats.2017.56 · Cited by 799 · see citing works
Mendes, B. B., Conniot, J., Avital, A., Yao, D., Jiang, X., Zhou, X., Sharf-Pauker, N., Xiao, Y., Adir, O., Liang, H., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00104-y · Cited by 719 · 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
Kim, J., Eygeris, Y., Gupta, M., & Sahay, G. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.12.014 · Cited by 514 · see citing works
The challenge and prospect of mRNA therapeutics landscape
Weng, Y., Li, C., Yang, T., Hu, B., Zhang, M., Guo, S., Xiao, H., Liang, X.-J., & Huang, Y. (2020) · Biotechnology Advances · doi:10.1016/j.biotechadv.2020.107534 · Cited by 417 · see citing works
Lipid nanoparticle technology for therapeutic gene regulation in the liver
Witzigmann, D., Kulkarni, J. A., Leung, J., Chen, S., Cullis, P. R., & van der Meel, R. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.06.026 · Cited by 376 · see citing works
Synergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver
Miao, L., Lin, J., Huang, Y., Li, L., Delcassian, D., Ge, Y., Shi, Y., & Anderson, D. G. (2020) · Nature Communications · doi:10.1038/s41467-020-16248-y · Cited by 343 · see citing works
Evers, M. J. W., Kulkarni, J. A., van der Meel, R., Cullis, P. R., Vader, P., & Schiffelers, R. M. (2018) · Small Methods · doi:10.1002/smtd.201700375 · Cited by 332 · see citing works
Kong, N., Tao, W., Ling, X., Wang, J., Xiao, Y., Shi, S., Ji, X., Shajii, A., Gan, S. T., Kim, N. Y., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw1565 · Cited by 314 · see citing works
Systemic Messenger RNA Therapy as a Treatment for Methylmalonic Acidemia
An, D., Schneller, J. L., Frassetto, A., Liang, S., Zhu, X., Park, J.-S., Theisen, M., Hong, S.-J., Zhou, J., Rajendran, R., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.081 · Cited by 263 · see citing works
Lipid nanoparticles for delivery of messenger RNA to the back of the eye
Patel, S., Ryals, R. C., Weller, K. K., Pennesi, M. E., & Sahay, G. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.04.015 · Cited by 260 · 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
mRNA Delivery for Therapeutic Anti-HER2 Antibody Expression In Vivo
Rybakova, Y., Kowalski, P. S., Huang, Y., Gonzalez, J. T., Heartlein, M. W., DeRosa, F., Delcassian, D., & Anderson, D. G. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.05.012 · Cited by 218 · see citing works
Lipid-based nanoparticle formulations for small molecules and RNA drugs
Ickenstein, L. M., & Garidel, P. (2019) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2019.1669558 · Cited by 193 · see citing works
de Alwis, R., Gan, E. S., Chen, S., Leong, Y. S., Tan, H. C., Zhang, S. L., Yau, C., Low, J. G. H., Kalimuddin, S., Matsuda, D., et al. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.04.001 · Cited by 191 · see citing works
Self-citationNanoscale platforms for messenger RNA delivery
Li, B., Zhang, X., & Dong, Y. (2019) · WIREs Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1530 · Cited by 170 · see citing works
mRNA mediates passive vaccination against infectious agents, toxins, and tumors
Thran, M., Mukherjee, J., Pönisch, M., Fiedler, K., Thess, A., Mui, B. L., Hope, M. J., Tam, Y. K., Horscroft, N., Heidenreich, R., et al. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707678 · Cited by 166 · see citing works
“Of note, equal or even higher levels were considered unproblematic in a recent study on modified mRNA encoding factor IX (Ramaswamy et al, 2017).”
BackgroundTruong, B., Allegri, G., Liu, X.-B., Burke, K. E., Zhu, X., Cederbaum, S. D., Häberle, J., Martini, P. G. V., & Lipshutz, G. S. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1906182116 · Cited by 151 · see citing works
Targeted mRNA Therapy for Ornithine Transcarbamylase Deficiency
Prieve, M. G., Harvie, P., Monahan, S. D., Roy, D., Li, A. G., Blevins, T. L., Paschal, A. E., Waldheim, M., Bell, E. C., Galperin, A., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2017.12.024 · Cited by 145 · see citing works
Van der Jeught, K., De Koker, S., Bialkowski, L., Heirman, C., Tjok Joe, P., Perche, F., Maenhout, S., Bevers, S., Broos, K., Deswarte, K., et al. (2018) · ACS Nano · doi:10.1021/acsnano.8b00966 · Cited by 139 · see citing works
Nanomedicine-Based Approaches for mRNA Delivery
Uchida, S., Perche, F., Pichon, C., & Cabral, H. (2020) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00618 · Cited by 139 · see citing works
Haabeth, O. A. W., Blake, T. R., McKinlay, C. J., Tveita, A. A., Sallets, A., Waymouth, R. M., Wender, P. A., & Levy, R. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2867 · Cited by 129 · see citing works
Nanoplatforms for mRNA Therapeutics
Meng, C., Chen, Z., Li, G., Welte, T., & Shen, H. (2021) · Advanced Therapeutics · doi:10.1002/adtp.202000099 · Cited by 130 · see citing works
Biomedical applications of mRNA nanomedicine
Xiong, Q., Lee, G. Y., Ding, J., Li, W., & Shi, J. (2018) · Nano Research · doi:10.1007/s12274-018-2146-1 · Cited by 125 · see citing works
Tanaka, H., Takahashi, T., Konishi, M., Takata, N., Gomi, M., Shirane, D., Miyama, R., Hagiwara, S., Yamasaki, Y., Sakurai, Y., et al. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201910575 · Cited by 126 · see citing works
Delivery of mRNA Therapeutics for the Treatment of Hepatic Diseases
Trepotec, Z., Lichtenegger, E., Plank, C., Aneja, M. K., & Rudolph, C. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2018.12.012 · Cited by 115 · see citing works
Non-immunotherapy application of LNP-mRNA: Maximizing efficacy and safety
Vlatkovic, I. (2021) · Biomedicines · doi:10.3390/biomedicines9050530 · Cited by 112 · see citing works
Recent Developments in mRNA-Based Protein Supplementation Therapy to Target Lung Diseases
Sahu, I., Haque, A. K. M. A., Weidensee, B., Weinmann, P., & Kormann, M. S. D. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.02.019 · Cited by 104 · see citing works
Treatment of Hemophilia A Using Factor VIII Messenger RNA Lipid Nanoparticles
Chen, C.-Y., Tran, D. M., Cavedon, A., Cai, X., Rajendran, R., Lyle, M. J., Martini, P. G. V., & Miao, C. H. (2020) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2020.03.015 · Cited by 89 · see citing works
Long-term efficacy and safety of mRNA therapy in two murine models of methylmalonic acidemia
An, D., Frassetto, A., Jacquinet, E., Eybye, M., Milano, J., DeAntonis, C., Nguyen, V., Laureano, R., Milton, J., Sabnis, S., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.07.003 · Cited by 87 · see citing works
Huysmans, H., Zhong, Z., De Temmerman, J., Mui, B. L., Tam, Y. K., Mc Cafferty, S., Gitsels, A., Vanrompay, D., & Sanders, N. N. (2019) · Molecular Therapy - Nucleic Acids · doi:10.1016/j.omtn.2019.08.001 · Cited by 83 · 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
In vitro evolution of enhanced RNA replicons for immunotherapy
Li, Y., Teague, B., Zhang, Y., Su, Z., Porter, E., Dobosh, B., Wagner, T., Irvine, D. J., & Weiss, R. (2019) · Scientific Reports · doi:10.1038/s41598-019-43422-0 · Cited by 71 · see citing works
Guevara, M. L., Jilesen, Z., Stojdl, D., & Persano, S. (2019) · ACS Omega · doi:10.1021/acsomega.9b00489 · Cited by 58 · see citing works
Systemic modified messenger RNA for replacement therapy in alpha 1-antitrypsin deficiency
Karadagi, A., Cavedon, A. G., Zemack, H., Nowak, G., Eybye, M. E., Zhu, X., Guadagnin, E., White, R. A., Rice, L. M., Frassetto, A. L., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-64017-0 · Cited by 54 · see citing works
Milbank, E., Díaz-Trelles, R., Dragano, N., Latorre, J., Mukthavaram, R., Mayneris-Perxachs, J., Ortega, F., Federici, M., Burcelin, R., Karmali, P. P., et al. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2022.106562 · Cited by 26 · see citing works
Self-citationAdvancing mRNA technologies for therapies and vaccines: An African context
Kairuz, D., Samudh, N., Ely, A., Arbuthnot, P., & Bloom, K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1018961 · Cited by 25 · 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
mRNA treatment produces sustained expression of enzymatically active human ADAMTS13 in mice
Liu-Chen, S., Connolly, B., Cheng, L., Subramanian, R. R., & Han, Z. (2018) · Scientific Reports · doi:10.1038/s41598-018-26298-4 · Cited by 20 · see citing works
- Authors
- Ramaswamy, S., Tonnu, N., Tachikawa, K., Limphong, P., Vega, J. B., Karmali, P. P., Chivukula, P., & Verma, I. M.
- Affiliations
- Salk Institute for Biological Studies (US)
- Arcturus Therapeutics (United States) (US)
- Corresponding author
- Verma, Inder M.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-02-15
- Volume
- 114
- Issue
- 10
- Pages
- E1941-E1950
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5347596
- OpenAlex
- W2587871737
- Cited by
- 301
- References
- 28
- Citations by year
- 2026: 23 · 2025: 28 · 2024: 36 · 2023: 37 · 2022: 45 · 2021: 35 · 2020: 34 · 2019: 28 · 2018: 28 · 2017: 7
- FWCI
- 20.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Cancer Institute (CCSG: P30 014195, NINDS, P30 CA014195-38)
- Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002)
- California Institute for Regenerative Medicine (CIRM-TR4-06809)
- Topics
- Health Sciences › Medicine › Hematology › Hemophilia Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- factor IX, mRNA therapeutics, lipid nanoparticles, hemophilia B, protein replacement therapy, systemic drug delivery, immune response, recombinant factor IX, clotting disorders, liver disease
- MeSH terms
- Animals, Cholesterol, Hemophilia B, Disease Models, Animal, Drug Carriers, Drug Compounding, Drug Evaluation, Preclinical, Factor IX, Female, Humans, Hydrogen-Ion Concentration, Injections, Intravenous, Liver, Male, Phosphatidylcholines, Recombinant Proteins, RNA, Messenger, Genetic Therapy, Cytokines, Mice, Knockout, Mice, Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
