The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs

Liposomal drug delivery systems: From concept to clinical applications

Allen, T. M., & Cullis, P. R. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.037 · Cited by 4,839 · see citing works

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

Rational design of cationic lipids for siRNA delivery

Semple, S. C., Akinc, A., Chen, J., Sandhu, A. P., Mui, B. L., Cho, C. K., Sah, D. W. Y., Stebbing, D., Crosley, E. J., Yaworski, E., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1602 · Cited by 1,822 · see citing works

RNAi-mediated gene silencing in non-human primates

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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

Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes

Pardi, N., Tuyishime, S., Muramatsu, H., Kariko, K., Mui, B. L., Tam, Y. K., Madden, T. D., Hope, M. J., & Weissman, D. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.007 · Cited by 1,014 · see citing works

Safety and efficacy of RNAi therapy for transthyretin amyloidosis

Coelho, T., Adams, D., Silva, A., Lozeron, P., Hawkins, P. N., Mant, T., Perez, J., Chiesa, J., Warrington, S., Tranter, E., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1208760 · Cited by 971 · see citing works

Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination

Pardi, N., Hogan, M. J., Pelc, R. S., Muramatsu, H., Andersen, H., DeMaso, C. R., Dowd, K. A., Sutherland, L. L., Scearce, R. M., Parks, R., et al. (2017) · Nature · doi:10.1038/nature21428 · Cited by 884 · see citing works

A Single Administration of CRISPR/Cas9 Lipid Nanoparticles Achieves Robust and Persistent In Vivo Genome Editing

Finn, J. D., Smith, A. R., Patel, M. C., Shaw, L., Youniss, M. R., van Heteren, J., Dirstine, T., Ciullo, C., Lescarbeau, R., Seitzer, J., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.014 · Cited by 878 · see citing works

Microfluidic Synthesis of Highly Potent Limit-size Lipid Nanoparticles for In Vivo Delivery of siRNA

Belliveau, N. M., Huft, J., Lin, P. J., Chen, S., Leung, A. K., Leaver, T. J., Wild, A. W., Lee, J. B., Taylor, R. J., Tam, Y. K., et al. (2012) · Molecular Therapy - Nucleic Acids · doi:10.1038/mtna.2012.28 · Cited by 685 · see citing works

On the formation and morphology of lipid nanoparticles containing ionizable cationic lipids and siRNA

Kulkarni, J. A., Darjuan, M. M., Mercer, J. E., Chen, S., van der Meel, R., Thewalt, J. L., Tam, Y. Y. C., & Cullis, P. R. (2018) · ACS Nano · doi:10.1021/acsnano.8b01516 · Cited by 663 · see citing works

On the mechanism whereby cationic lipids promote intracellular delivery of polynucleic acids

Hafez, I., Maurer, N., & Cullis, P. R. (2001) · Gene Therapy · doi:10.1038/sj.gt.3301506 · Cited by 601 · see citing works

Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals

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

Influence of Polyethylene Glycol Lipid Desorption Rates on Pharmacokinetics and Pharmacodynamics of siRNA Lipid Nanoparticles

Mui, B. L., Tam, Y. K., Jayaraman, M., Ansell, S. M., Du, X., Tam, Y. Y. C., Lin, P. J. C., Chen, S., Narayanannair, J. K., Rajeev, K. G., et al. (2013) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2013.66 · Cited by 509 · see citing works

Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids: formation of novel small multilamellar vesicle structures

Semple, S. C., Klimuk, S. K., Harasym, T. O., Dos Santos, N., Ansell, S. M., Wong, K. F., Maurer, N., Stark, H., Cullis, P. R., Hope, M. J., et al. (2001) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(00)00343-6 · Cited by 454 · see citing works

Microfluidic Mixing: A General Method for Encapsulating Macromolecules in Lipid Nanoparticle Systems

Leung, A. K. K., Tam, Y. Y. C., Chen, S., Hafez, I. M., & Cullis, P. R. (2015) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.5b02891 · Cited by 359 · see citing works

Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge

Pardi, N., Secreto, A. J., Shan, X., Debonera, F., Glover, J., Yi, Y., Muramatsu, H., Ni, H., Mui, B. L., Tam, Y. K., et al. (2017) · Nature Communications · doi:10.1038/ncomms14630 · Cited by 352 · see citing works

Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies

Pardi, N., Parkhouse, K., Kirkpatrick, E., McMahon, M., Zost, S. J., Mui, B. L., Tam, Y. K., Karikó, K., Barbosa, C. J., Madden, T. D., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05482-0 · Cited by 281 · see citing works

Fusion-dependent formation of lipid nanoparticles containing macromolecular payloads

Kulkarni, J. A., Witzigmann, D., Leung, J., van der Meel, R., Zaifman, J., Darjuan, M. M., Grisch-Chan, H. M., Thöny, B., Tam, Y. Y. C., & Cullis, P. R. (2019) · Nanoscale · doi:10.1039/c9nr02004g · Cited by 161 · see citing works

Generating and loading of liposomal systems for drug-delivery applications

Cullis, P. R., Mayer, L. D., Bally, M. B., Madden, T. D., & Hope, M. J. (1989) · Advanced Drug Delivery Reviews · doi:10.1016/0169-409x(89)90024-0 · Cited by 96 · see citing works

Non-viral Delivery of Zinc Finger Nuclease mRNA Enables Highly Efficient In Vivo Genome Editing of Multiple Therapeutic Gene Targets

Conway, A., Mendel, M., Kim, K., McGovern, K., Boyko, A., Zhang, L., Miller, J. C., DeKelver, R. C., Paschon, D. E., Mui, B. L., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.03.003 · Cited by 95 · see citing works

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

Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing

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

Lipid NanoparticlesFrom Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement

Tenchov, R., Bird, R., Curtze, A. E., & Zhou, Q. (2021) · ACS Nano · doi:10.1021/acsnano.1c04996 · Cited by 2,221 · see citing works

CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis

Gillmore, J. D., Gane, E., Taubel, J., Kao, J., Fontana, M., Maitland, M. L., Seitzer, J., O’Connell, D., Walsh, K. R., Wood, K., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2107454 · Cited by 1,766 · see citing works

The evolution of commercial drug delivery technologies

Vargason, A. M., Anselmo, A. C., & Mitragotri, S. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00698-w · Cited by 1,361 · see citing works

Smart nanoparticles for cancer therapy

Sun, L., Liu, H., Ye, Y., Lei, Y., Islam, R., Tan, S., Tong, R., Miao, Y.-B., & Cai, L. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01642-x · Cited by 1,073 · see citing works

Nanodelivery of nucleic acids

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

Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR–Cas gene editing

Liu, S., Cheng, Q., Wei, T., Yu, X., Johnson, L. T., Farbiak, L., & Siegwart, D. J. (2021) · Nature Materials · doi:10.1038/s41563-020-00886-0 · Cited by 653 · see citing works

Advances in COVID-19 mRNA vaccine development

Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601 · see citing works

Nanomaterial Delivery Systems for mRNA Vaccines

Buschmann, M. D., Carrasco, M. J., Alishetty, S., Paige, M., Alameh, M. G., & Weissman, D. (2021) · Vaccines · doi:10.3390/vaccines9010065 · Cited by 582 · see citing works

Self-assembled mRNA vaccines

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 dawn of mRNA vaccines: the COVID-19 case

Verbeke, R., Lentacker, I., De Smedt, S. C., & Dewitte, H. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.03.043 · Cited by 504 · see citing works

A Comprehensive Review of mRNA Vaccines

Gote, V., Bolla, P. K., Kommineni, N., Butreddy, A., Nukala, P. K., Palakurthi, S. S., & Khan, W. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032700 · Cited by 457 · 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

Apolipoprotein E binding drives structural and compositional rearrangement of mRNA-containing lipid nanoparticles

Sebastiani, F., Yanez Arteta, M., Lerche, M., Porcar, L., Lang, C., Bragg, R. A., Elmore, C. S., Krishnamurthy, V. R., Russell, R. A., Darwish, T., et al. (2021) · ACS Nano · doi:10.1021/acsnano.0c10064 · Cited by 409 · see citing works

Cytosolic delivery of nucleic acids: The case of ionizable lipid nanoparticles

Schlich, M., Palomba, R., Costabile, G., Mizrahy, S., Pannuzzo, M., Peer, D., & Decuzzi, P. (2021) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10213 · Cited by 387 · 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

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

An Update on Self-Amplifying mRNA Vaccine Development

Blakney, A. K., Ip, S., & Geall, A. J. (2021) · Vaccines · doi:10.3390/vaccines9020097 · Cited by 288 · see citing works

Metallodrugs in cancer nanomedicine

Peña, Q., Wang, A., Zaremba, O., Shi, Y., Scheeren, H. W., Metselaar, J. M., Kiessling, F., Pallares, R. M., Wuttke, S., & Lammers, T. (2022) · Chemical Society Reviews · doi:10.1039/d1cs00468a · Cited by 259 · see citing works

Polysarcosine-functionalized lipid nanoparticles for therapeutic mRNA delivery

Nogueira, S. S., Schlegel, A., Maxeiner, K., Weber, B., Barz, M., Schroer, M. A., Blanchet, C. E., Svergun, D. I., Ramishetti, S., Peer, D., et al. (2020) · ACS Applied Nano Materials · doi:10.1021/acsanm.0c01834 · Cited by 252 · see citing works

Lipid nanoparticle-mediated drug delivery to the brain

Khare, P., Edgecomb, S. X., Hamadani, C. M., Tanner, E. E. L., & S Manickam, D. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114861 · Cited by 187 · see citing works

Biomembrane-based nanostructures for cancer targeting and therapy: From synthetic liposomes to natural biomembranes and membrane-vesicles

Wang, J., Zhu, M., & Nie, G. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113974 · Cited by 153 · see citing works

Leveraging mRNA Sequences and Nanoparticles to Deliver SARS‐CoV‐2 Antigens In Vivo

Zeng, C., Hou, X., Yan, J., Zhang, C., Li, W., Zhao, W., Du, S., & Dong, Y. (2020) · Advanced Materials · doi:10.1002/adma.202004452 · Cited by 152 · see citing works

Hepatic macrophage targeted siRNA lipid nanoparticles treat non-alcoholic steatohepatitis

Zhou, J.-E., Sun, L., Liu, L., Jia, Y., Han, Y., Shao, J., Wang, J., Wang, Y., Yu, L., & Yan, Z. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.01.038 · Cited by 104 · see citing works

Drug Delivery Across the Blood–Brain Barrier: A New Strategy for the Treatment of Neurological Diseases

Jiao, Y., Yang, L., Wang, R., Song, G., Fu, J., Wang, J., Gao, N., & Wang, H. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16121611 · Cited by 63 · see citing works

Naturally Derived Membrane Lipids Impact Nanoparticle-Based Messenger RNA Delivery

Kim, J., Jozic, A., & Sahay, G. (2020) · Cellular and Molecular Bioengineering · doi:10.1007/s12195-020-00619-y · Cited by 61 · see citing works

Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning

Luo, J., Molbay, M., Chen, Y., Horvath, I., Kadletz, K., Kick, B., Zhao, S., Al-Maskari, R., Singh, I., Ali, M., et al. (2025) · Nature Biotechnology · doi:10.1038/s41587-024-02528-1 · Cited by 53 · see citing works

Development of Novel siRNA Therapeutics: A Review with a Focus on Inclisiran for the Treatment of Hypercholesterolemia

Ebenezer, 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

Advancing 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

From bench side to clinic: Potential and challenges of RNA vaccines and therapeutics in infectious diseases

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

Production, Characterization, and Assessment of Permanently Cationic and Ionizable Lipid Nanoparticles for Use in the Delivery of Self-Amplifying RNA Vaccines

Kairuz, D., Samudh, N., Ely, A., Arbuthnot, P., & Bloom, K. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041173 · Cited by 17 · see citing works

Targeting DNA damage repair mechanism by using RAD50-silencing siRNA nanoparticles to enhance radiotherapy in triple negative breast cancer

Zetrini, A. E., Abbasi, A. Z., He, C., Lip, H., Alradwan, I., Rauth, A. M., Henderson, J. T., & Wu, X. Y. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101206 · Cited by 12 · see citing works

siRNA Nanoparticle Delivery Strategies and Clinical Trial Advances in Tumor Therapy

Wang, P., Gong, J., Xu, Y., & Xia, X. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27073032 · Cited by 4 · see citing works

Advancing cancer radiotherapy: Harnessing radiosensitizers and nanotechnology for enhanced tumor control

Shiridokht, F., Kehtari, P., Eskandani, M., Farajollahi, A., & Vandghanooni, S. (2025) · International Journal of Pharmaceutics: X · doi:10.1016/j.ijpx.2025.100419 · Cited by 4 · see citing works

Multiplex screening of transferrin receptor-targeted lipid nanoparticles for systemic brain delivery using DNA barcodes

Ghosh, S., Fan, Y., Laufer, B. I., Stephenson, W., Zang, N., Lawrence, J., Lin, H. H., Sen, S., Miller, S. E., Chu, S., et al. (2026) · Cell Biomaterials · doi:10.1016/j.celbio.2025.100303 · Cited by 3 · see citing works

High-density Lipoprotein Inspired Lipid Nanoparticles for Systemic RNA delivery to the Brain

Xu, Z., Shalin, K., Do, V., Yan, A., & Gao, J. (2026) · doi:10.64898/2026.05.29.728695

Transthyretin is synthesized in the mammalian eye

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Variant transthyretin in cerebrospinal fluid in familial amyloidotic polyneuropathy

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Transthyretin (prealbumin) gene expression in choroid plexus is strongly conserved during evolution of vertebrates

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Presence of variant transthyretin in aqueous humor of a patient with familial amyloidotic polyneuropathy after liver transplantation

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