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Targeted Delivery of RNAi Therapeutics With Endogenous and Exogenous Ligand-Based Mechanisms
Open accessAbstract
Lipid nanoparticles (LNPs) have proven to be highly efficient carriers of short-interfering RNAs (siRNAs) to hepatocytes in vivo; however, the precise mechanism by which this efficient delivery occurs has yet to be elucidated. We found that apolipoprotein E (apoE), which plays a major role in the clearance and hepatocellular uptake of physiological lipoproteins, also acts as an endogenous targeting ligand for ionizable LNPs (iLNPs), but not cationic LNPs (cLNPs). The role of apoE was investigated using both in vitro studies employing recombinant apoE and in vivo studies in wild-type and apoE(-/-) mice. Receptor dependence was explored in vitro and in vivo using low-density lipoprotein receptor (LDLR(-/-))-deficient mice. As an alternative to endogenous apoE-based targeting, we developed a targeting approach using an exogenous ligand containing a multivalent N-acetylgalactosamine (GalNAc)-cluster, which binds with high affinity to the asialoglycoprotein receptor (ASGPR) expressed on hepatocytes. Both apoE-based endogenous and GalNAc-based exogenous targeting appear to be highly effective strategies for the delivery of iLNPs to liver.
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“At blood pH, LNPs exhibit a net neutral surface charge but become positively charged in acidified endosomes following ApoE-mediated endocytosis by hepatocytes in vivo, resulting in endosome disruption and release of mRNA into the cytoplasm.28,41,45”
From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [45]
In the citing paper
“Previous work has shown that LNP systems with this lipid composition can silence target genes in hepatocytes following IV injection at dose levels as low as 0.01 mg siRNA/kg body weight8,9 in an apolipoprotein E (ApoE)–dependent fashion.10”
From Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain (2013) · cites this paper as [10]
In the citing paper
“Detailed studies have shown that the ability of LNP-siRNA systems containing related ionizable cationic lipids to induce hepatocyte gene knockdown in vivo is ApoE dependent.10”
From Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain (2013) · cites this paper as [10]
In the citing paper
“In ApoE knockout mice, LNP-siRNA gene silencing activity is inhibited in hepatocytes and can be reestablished by incubating the LNPs with ApoE before IV administration.”
From Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain (2013) · cites this paper as [10]
In the citing paper
“Upon intravenous administration, Akinc et al. found that the surface of neutrally-charged LNPs is strongly enriched with apolipoprotein E (ApoE), which leads to enhanced uptake by hepatocytes through low density lipoprotein (LDL) receptor-mediated endocytosis [40]”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [40]
In the citing paper
“As example, Akinc et al. found that the selective adsorption of apolipoprotein E onto an ionizable (neutral) LNP was responsible for the specific and potent delivery of (si)RNA to hepatocytes through receptor mediated endocytosis [156].”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [156]
In the citing paper
“one potential mechanism of hepatocyte targeting effect by LNPs involves the interaction of ionizable LNPs with apolipoprotein E (apoE), a protein that facilitates the transport of molecules such as lipids and cholesterol.[59, 60] Binding on the surface of LNPs, apoE mediated the hepatocellular uptake of LNPs through multiple receptors, such as the low-density lipoprotein receptor (LDLR).[59, 60]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [60]
Citations
Cites
Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
Mahley, R. W. (1988) · Science · doi:10.1126/science.3283935 · Cited by 4,028
New-Concept Chemotherapy by Nanoparticles of Biodegradable Polymers: Where Are We Now?
Feng, S.-S. (2006) · Nanomedicine · doi:10.2217/17435889.1.3.297 · Cited by 1,951
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
Allen, T. M., Hansen, C., Martin, F., Redemann, C. T., & Yau‐Young, A. O. (1991) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(91)90246-5 · Cited by 1,392
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
A combinatorial library of lipid-like materials for delivery of RNAi therapeutics
Akinc, A., Zumbuehl, A., Goldberg, M., Leshchiner, E. S., Busini, V., Hossain, N., Bacallado, S. A., Nguyen, D. N., Fuller, J., Alvarez, R., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1402 · Cited by 1,150
Lipid-like materials for low-dose, in vivo gene silencing
Love, K. T., Mahon, K. P., Levins, C. G., Whitehead, K. A., Querbes, W., Dorkin, J. R., Qin, J., Cantley, W., Qin, L. L., Racie, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910603106 · Cited by 969
Mahley, R. W., & Ji, Z.-S. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)33334-4 · Cited by 693
The LDL–receptor–related protein, LRP, is an apolipoprotein E-binding protein
Beisiegel†, U., Weber, W. T., Ihrke, G., Herz, J., & Stanley, K. K. (1989) · Nature · doi:10.1038/341162a0 · Cited by 680
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 644
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- Immordino, 2006, Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential, Int J Nanomedicine, 1, 297
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Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.243 · Cited by 4,667
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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
Self-citationCheng, 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
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Roberts, T. C., Langer, R., & Wood, M. J. A. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0075-7 · Cited by 2,121
Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter
Baughman, J. M., Perocchi, F., Girgis, H. S., Plovanich, M., Belcher-Timme, C. A., Sancak, Y., Bao, X. R., Strittmatter, L., Goldberger, O., Bogorad, R. L., et al. (2011) · Nature · doi:10.1038/nature10234 · Cited by 1,953
Delivery materials for siRNA therapeutics
Kanasty, R., Dorkin, J. R., Vegas, A., & Anderson, D. (2013) · Nature Materials · doi:10.1038/nmat3765 · Cited by 1,800
Self-citationGilleron, J., Querbes, W., Zeigerer, A., Borodovsky, A., Marsico, G., Schubert, U., Manygoats, K., Seifert, S., Andree, C., Stöter, M., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2612 · Cited by 1,681
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
Therapeutic siRNA: state of the art
Hu, B., Zhong, L., Weng, Y., Peng, L., Huang, Y., Zhao, Y., & Liang, X.-J. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0207-x · Cited by 1,586
The current state and future directions of RNAi-based therapeutics
Setten, R. L., Rossi, J. J., & Han, S.-P. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0017-4 · Cited by 1,443
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Kulkarni, J. A., Witzigmann, D., Thomson, S. B., Chen, S., Leavitt, B. R., Cullis, P. R., & van der Meel, R. (2021) · Nature Nanotechnology · doi:10.1038/s41565-021-00898-0 · Cited by 1,371
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Paunovska, K., Loughrey, D., & Dahlman, J. E. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00439-4 · Cited by 1,349
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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
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Gregersen, C. H., Kulkarni, J. A., Witzigmann, D., Lind, M. L., Petersson, K., & Simonsen, J. B. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114416 · Cited by 1,271
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Cullis, P. R., & Hope, M. J. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.03.013 · Cited by 1,208
Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery
Lee, H., Lytton‐Jean, A. K. R., Chen, Y., Love, K. T., Park, A. I., Karagiannis, E. D., Sehgal, A., Querbes, W., Zurenko, C., Jayaraman, M., et al. (2012) · Nature Nanotechnology · doi:10.1038/nnano.2012.73 · Cited by 1,168
Treating metastatic cancer with nanotechnology
Schroeder, A., Heller, D. A., Winslow, M. M., Dahlman, J. E., Pratt, G. W., Langer, R., Jacks, T., & Anderson, D. G. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3180 · Cited by 1,175
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
Therapeutic targeting of microRNAs: current status and future challenges
Li, Z., & Rana, T. M. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4359 · Cited by 1,052
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
On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles
Dilliard, S. A., Cheng, Q., & Siegwart, D. J. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2109256118 · Cited by 1,018
Mechanism of hard-nanomaterial clearance by the liver
Tsoi, K. M., MacParland, S. A., Ma, X., Spetzler, V. N., Echeverri, J. A., Ouyang, B., Fadel, S. M., Sykes, E. A., Goldaracena, N., Kaths, J. M., et al. (2016) · Nature Materials · doi:10.1038/nmat4718 · Cited by 1,035
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Tibbitt, M. W., Dahlman, J. E., & Langer, R. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.5b09974 · Cited by 1,009
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
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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
The delivery of therapeutic oligonucleotides
Juliano, R. L. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw236 · Cited by 882
The clinical progress of mRNA vaccines and immunotherapies
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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
Knocking down disease: a progress report on siRNA therapeutics
Wittrup, A., & Lieberman, J. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3978 · Cited by 827
The journey of a drug-carrier in the body: An anatomo-physiological perspective
Bertrand, N., & Leroux, J. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.09.098 · Cited by 737
Bertrand, N., Grenier, P., Mahmoudi, M., Lima, E. M., Appel, E. A., Dormont, F., Lim, J.-M., Karnik, R., Langer, R., & Farokhzad, O. C. (2017) · Nature Communications · doi:10.1038/s41467-017-00600-w · Cited by 708
Tabernero, J. M., Shapiro, G. I., LoRusso, P. M., Cervantes, A. M. R., Schwartz, G. K., Weiss, G. J., Paz-Ares, L. G., Cho, D. C., Infante, J. R., Alsina, M., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0429 · Cited by 717
Visualizing 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
Self-citationDilliard, S. A., & Siegwart, D. J. (2023) · Nature Reviews Materials · doi:10.1038/s41578-022-00529-7 · Cited by 744
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Zhang, Y., Sun, C., Wang, C., Jankovic, K. E., & Dong, Y. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00244 · Cited by 649
An ionizable lipid toolbox for RNA delivery
Han, X., Zhang, H., Butowska, K., Swingle, K. L., Alameh, M.-G., Weissman, D., & Mitchell, M. J. (2021) · Nature Communications · doi:10.1038/s41467-021-27493-0 · Cited by 628
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
Unlocking the promise of mRNA therapeutics
Rohner, E., Yang, R., Foo, K. S., Goedel, A., & Chien, K. R. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01491-z · Cited by 612
In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight
Dahlman, J. E., Barnes, C., Khan, O. F., Thiriot, A., Jhunjhunwala, S., Shaw, T. E., Xing, Y., Sager, H. B., Sahay, G., Speciner, L., et al. (2014) · Nature Nanotechnology · doi:10.1038/nnano.2014.84 · Cited by 597
Patel, S., Ashwanikumar, N., Robinson, E., Xia, Y., Mihai, C., Griffith, J. P., Hou, S., Esposito, A. A., Ketova, T., Welsher, K., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14527-2 · Cited by 601
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Bennett, C. F. (2019) · Annual Review of Medicine · doi:10.1146/annurev-med-041217-010829 · Cited by 609
Lipid nanoparticles for nucleic acid delivery: Current perspectives
Samaridou, E., Heyes, J. A., & Lutwyche, P. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.06.002 · Cited by 609
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Buschmann, M. D., Carrasco, M. J., Alishetty, S., Paige, M., Alameh, M. G., & Weissman, D. (2021) · Vaccines · doi:10.3390/vaccines9010065 · Cited by 582
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
Exosomes for targeted siRNA delivery across biological barriers
Andaloussi, S. E., Lakhal‐Littleton, S., Mäger, I., & Wood, M. J. A. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.08.008 · Cited by 555
Lipid Nanoparticle Technology for Clinical Translation of siRNA Therapeutics
Kulkarni, J. A., Witzigmann, D., Chen, S., Cullis, P. R., & van der Meel, R. (2019) · Accounts of Chemical Research · doi:10.1021/acs.accounts.9b00368 · Cited by 556
New Vaccine Technologies to Combat Outbreak Situations
Rauch, S., Jasny, E., Schmidt, K. E., & Petsch, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01963 · Cited by 579
The 60-year evolution of lipid nanoparticles for nucleic acid delivery
Cullis, P. R., & Felgner, P. L. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-00977-6 · Cited by 583
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
Kim, J., Eygeris, Y., Gupta, M., & Sahay, G. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.12.014 · Cited by 514
Innate immune mechanisms of mRNA vaccines
Verbeke, R., Hogan, M. J., Loré, K., & Pardi, N. (2022) · Immunity · doi:10.1016/j.immuni.2022.10.014 · Cited by 535
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
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
Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates
Dong, Y., Love, K. T., Dorkin, J. R., Sirirungruang, S., Zhang, Y., Chen, D., Bogorad, R. L., Yin, H., Chen, Y., Vegas, A. J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322937111 · Cited by 488
Self-citationExtracellular vesicles as drug delivery systems: Lessons from the liposome field
van der Meel, R., Fens, M. H. A. M., Vader, P., van Solinge, W. W., Eniola‐Adefeso, O., & Schiffelers, R. M. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.07.049 · Cited by 498
Plovanich, M., Bogorad, R. L., Sancak, Y., Kamer, K. J., Strittmatter, L., Li, A. A., Girgis, H. S., Kuchimanchi, S., Groot, J. D., Speciner, L., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055785 · Cited by 463
Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease
Adams, D., Koike, H., Slama, M., & Coelho, T. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0210-4 · Cited by 469
Carrasco, M. J., Alishetty, S., Alameh, M., Said, H., Wright, L., Paige, M. A., Soliman, O. Y., Weissman, D., Cleveland, T. E., Grishaev, A., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02441-2 · Cited by 460
The Medicinal Chemistry of Therapeutic Oligonucleotides
Wan, W. B., & Seth, P. P. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00551 · Cited by 445
Chen, D., Love, K. T., Chen, Y., Eltoukhy, A. A., Kastrup, C. J., Sahay, G., Jeon, A., Dong, Y.-Z., Whitehead, K., & Anderson, D. G. (2012) · Journal of the American Chemical Society · doi:10.1021/ja301621z · Cited by 386
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
Brief update on endocytosis of nanomedicines
Patel, S., Kim, J., Herrera‐Barrera, M., Mukherjee, A., Kabanov, A. V., & Sahay, G. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.08.004 · Cited by 409
Materials for non-viral intracellular delivery of messenger RNA therapeutics
Kauffman, K. J., Webber, M. J., & Anderson, D. G. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.12.032 · Cited by 407
Kim, 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
Delivery of oligonucleotide‐based therapeutics: challenges and opportunities
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“In addition, active hepatocyte targeting has been shown to occur via surface adsorption of apolipoprotein E, which targets the LNPs to the internalising low-density lipoprotein receptor expressed on hepatocytes (Akinc et al, 2010; Chen et al, 2016).”
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Phosphorothioate modified oligonucleotide–protein interactions
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Kon, E., Ad‐El, N., Hazan‐Halevy, I., Stotsky‐Oterin, L., & Peer, D. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00811-9 · Cited by 393
Influence of particle size on the in vivo potency of lipid nanoparticle formulations of siRNA
Chen, S., Tam, Y. Y. C., Lin, P. J. C., Sung, M. M. H., Tam, Y. K., & Cullis, P. R. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.05.059 · Cited by 366
Rab5 is necessary for the biogenesis of the endolysosomal system in vivo
Zeigerer, A., Gilleron, J., Bogorad, R. L., Marsico, G., Nonaka, H., Seifert, S., Epstein-Barash, H., Kuchimanchi, S., Peng, C. G., Ruda, V. M., et al. (2012) · Nature · doi:10.1038/nature11133 · Cited by 362
Self-citationMicrofluidic 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
In Vivo Gene Delivery by Nonviral Vectors: Overcoming Hurdles?
Zhang, Y., Satterlee, A., & Huang, L. (2012) · Molecular Therapy · doi:10.1038/mt.2012.79 · Cited by 361
Novel approaches for vaccine development
Gebre, M. S., Brito, L. A., Tostanoski, L. H., Edwards, D. K., Carfi, A., & Barouch, D. H. (2021) · Cell · doi:10.1016/j.cell.2021.02.030 · Cited by 347
Three decades of messenger RNA vaccine development
Verbeke, R., Lentacker, I., De Smedt, S. C., & Dewitte, H. (2019) · Nano Today · doi:10.1016/j.nantod.2019.100766 · Cited by 342
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
In vivo hematopoietic stem cell modification by mRNA delivery
Breda, L., Papp, T. E., Triebwasser, M. P., Yadegari, A., Fedorky, M. T., Tanaka, N., Abdulmalik, O. Y., Pavani, G., Wang, Y., Grupp, S. A., et al. (2023) · Science · doi:10.1126/science.ade6967 · Cited by 353
Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics
Dahlman, J. E., Kauffman, K. J., Xing, Y., Shaw, T. E., Mir, F. F., Dlott, C. C., Langer, R., Anderson, D. G., & Wang, E. T. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620874114 · Cited by 335
Antisense Oligonucleotide Therapies
Frazier, K. S. (2014) · Toxicologic Pathology · doi:10.1177/0192623314551840 · Cited by 335
Polymer–Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs
Kaczmarek, J. C., Patel, A. K., Kauffman, K. J., Fenton, O. S., Webber, M. J., Heartlein, M. W., DeRosa, F., & Anderson, D. G. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201608450 · Cited by 337
Lipid-Nanoparticle-Based Delivery of CRISPR/Cas9 Genome-Editing Components
Kazemian, P., Yu, S.-Y., Thomson, S. B., Birkenshaw, A., Leavitt, B. R., & Ross, C. J. (2022) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.1c00916 · Cited by 363
Nucleic acid delivery for therapeutic applications
Gupta, A., Andresen, J. L., Manan, R. S., & Langer, R. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113834 · Cited by 351
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
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
Lipid-Based DNA Therapeutics: Hallmarks of Non-Viral Gene Delivery
Buck, J., Grossen, P., Cullis, P. R., Huwyler, J., & Witzigmann, D. (2019) · ACS Nano · doi:10.1021/acsnano.8b07858 · Cited by 322
Polymers for siRNA Delivery: Inspired by Viruses to be Targeted, Dynamic, and Precise
Wagner, E. (2011) · Accounts of Chemical Research · doi:10.1021/ar2002232 · Cited by 309
Li, J., Yang, Y., & Huang, L. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.10.020 · Cited by 307
The Biomolecular Corona of Lipid Nanoparticles for Gene Therapy
Francia, V., Schiffelers, R. M., Cullis, P. R., & Witzigmann, D. (2020) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.0c00366 · Cited by 314
Suzuki, Y., & Ishihara, H. (2021) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2021.100424 · Cited by 323
Kenjo, E., Hozumi, H., Makita, Y., Iwabuchi, K. A., Fujimoto, N., Matsumoto, S., Kimura, M., Amano, Y., Ifuku, M., Naoe, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26714-w · Cited by 313
Baumann, V., & Winkler, J. (2014) · Future Medicinal Chemistry · doi:10.4155/fmc.14.116 · Cited by 309
Tombácz, I., Laczko, D. I., Shahnawaz, H., Muramatsu, H., Natesan, A., Yadegari, A., Papp, T. E., Alameh, M., Shuvaev, V. V., Mui, B. L., et al. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.06.004 · Cited by 300
Delivery Aspects of CRISPR/Cas for in Vivo Genome Editing
Wilbie, D., Walther, J., & Mastrobattista, E. (2019) · Accounts of Chemical Research · doi:10.1021/acs.accounts.9b00106 · Cited by 311
Payload distribution and capacity of mRNA lipid nanoparticles
Li, S., Hu, Y., Li, A. I., Lin, J., Hsieh, K., Schneiderman, Z., Zhang, P., Zhu, Y., Qiu, C., Kokkoli, E., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33157-4 · Cited by 299
Metadata
- Authors
- 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., Butler, J. S., Qin, L., Racie, T., Sprague, A., Fava, E., Zeigerer, A., Hope, M. J., Zerial, M., Sah, D. W., Fitzgerald, K., Tracy, M. A., Manoharan, M., Koteliansky, V., Fougerolles, A. D., & Maier, M. A.
- Affiliations
- Alnylam Pharmaceuticals (United States) (US)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- Corresponding author
- Akinc, Akin
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 18
- Issue
- 7
- Pages
- 1357-1364
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC2911264
- OpenAlex
- W2143743183
- Cited by
- 1,261
- References
- 32
- Citations by year
- 2026: 147 · 2025: 141 · 2024: 164 · 2023: 129 · 2022: 120 · 2021: 83 · 2020: 72 · 2019: 63 · 2018: 39 · 2017: 41 · 2016: 47 · 2015: 46 · 2014: 51 · 2013: 46 · 2012: 44
- FWCI
- 15.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Alnylam Pharmaceuticals
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- RNAi therapeutics, lipid nanoparticles, apolipoprotein E, N-acetylgalactosamine, asialoglycoprotein receptor, hepatocyte targeting, LDL receptor, nanoparticle clearance
- MeSH terms
- Animals, Apolipoproteins E, Female, HeLa Cells, Humans, Ligands, Mice, Inbred C57BL, Receptors, LDL, Hepatocytes, RNA Interference, Asialoglycoprotein Receptor, Mice, Nanoparticles
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