Boosting intracellular delivery of lipid nanoparticle-encapsulated mRNA
Open accessAbstract
Intracellular delivery of mRNA holds great potential for vaccine1-3 and therapeutic4 discovery and development. Despite increasing recognition of the utility of lipid-based nanoparticles (LNPs) for intracellular delivery of mRNA, particle engineering is hindered by insufficient understanding of endosomal escape, which is believed to be a main limiter of cytosolic availability and activity of the nucleic acid inside the cell. Using a series of CRISPR-based genetic perturbations of the lysosomal pathway, we have identified that late endosome/lysosome (LE/Ly) formation is essential for functional delivery of exogenously presented mRNA. Lysosomes provide a spatiotemporal hub to orchestrate mTOR signaling and are known to control cell proliferation, nutrient sensing, ribosomal biogenesis, and mRNA translation. Through modulation of the mTOR pathway we were able to enhance or inhibit LNP-mediated mRNA delivery. To further boost intracellular delivery of mRNA, we screened 212 bioactive lipid-like molecules that are either enriched in vesicular compartments or modulate cell signaling. Surprisingly, we have discovered that leukotriene-antagonists, clinically approved for treatment of asthma and other lung diseases, enhance intracellular mRNA delivery in vitro (over 3-fold, p < 0.005) and in vivo (over 2-fold, p < 0.005). Understanding LNP-mediated intracellular delivery will inspire the next generation of RNA therapeutics that have high potency and limited toxicity.
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?
Recruitment of the mechanistic target of rapamycin complex 1 to the lysosomal membrane is key to trigger translation of delivered mRNA.
“By contrast, the recruitment of the mechanistic target of rapamycin complex 1 to the lysosomal membrane was key to trigger the translation of delivered mRNA [122].”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [122]
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
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
Prostaglandins and Leukotrienes: Advances in Eicosanoid Biology
Funk, C. D. (2001) · Science · doi:10.1126/science.294.5548.1871 · Cited by 3,817 · see citing works
Rab proteins as membrane organizers
Zerial, M., & McBride, H. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35052055 · Cited by 3,381 · see citing works
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
Karikó, K., Buckstein, M., Ni, H., & Weissman, D. (2005) · Immunity · doi:10.1016/j.immuni.2005.06.008 · Cited by 2,728 · 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
Sahay, G., Alakhova, D. Y., & Kabanov, A. V. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.01.036 · Cited by 2,181 · see citing works
Self-citationA lysosome‐to‐nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB
Settembre, C., Zoncu, R., Medina, D. L., Vetrini, F., Erdin, S., Erdin, S. U., Huynh, T., Ferron, M., Karsenty, G., Vellard, M. C., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.32 · Cited by 1,932 · 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
Gilleron, 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 · see citing works
Endosomal escape pathways for delivery of biologicals
Varkouhi, A. K., Scholte, M., Storm, G., & Haisma, H. J. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.004 · Cited by 1,561 · see citing works
Batrakova, E. V., & Kabanov, A. V. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.04.013 · Cited by 1,278 · 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
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
Overcoming cellular barriers for RNA therapeutics
Dowdy, S. F. (2017) · Nature Biotechnology · doi:10.1038/nbt.3802 · Cited by 1,139 · see citing works
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
Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling
Sahay, G., Querbes, W., Alabi, C., Eltoukhy, A., Sarkar, S., Zurenko, C., Karagiannis, E., Love, K., Chen, D., Zoncu, R., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2614 · Cited by 948 · see citing works
Self-citationThe proton sponge: a trick to enter cells the viruses did not exploit
Behr, J.-P. (1997) · CHIMIA · doi:10.2533/chimia.1997.34 · Cited by 933 · 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
In vitro and ex vivo strategies for intracellular delivery
Stewart, M. P., Sharei, A., Ding, X., Sahay, G., Langer, R., & Jensen, K. F. (2016) · Nature · doi:10.1038/nature19764 · Cited by 885 · 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
The Lysosome as a Regulatory Hub
Perera, R. M., & Zoncu, R. (2016) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-125125 · Cited by 664 · 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
Self-citationPharmacological Inhibition of Endocytic Pathways: Is It Specific Enough to Be Useful?
Ivanov, A. I. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-178-9_2 · Cited by 605 · see citing works
The position of lysosomes within the cell determines their luminal pH
Johnson, D. E., Ostrowski, P., Jaumouillé, V., & Grinstein, S. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201507112 · Cited by 590 · see citing works
Cellular uptake and trafficking of antisense oligonucleotides
Crooke, S. T., Wang, S., Vickers, T. A., Shen, W., & Liang, X.-H. (2017) · Nature Biotechnology · doi:10.1038/nbt.3779 · Cited by 582 · see citing works
Lysosomal cholesterol activates mTORC1 via an SLC38A9–Niemann-Pick C1 signaling complex
Castellano, B. M., Thelen, A. M., Moldavski, O., Feltes, M., van der Welle, R. E. N., Mydock-McGrane, L., Jiang, X., van Eijkeren, R. J., Davis, O. B., Louie, S. M., et al. (2017) · Science · doi:10.1126/science.aag1417 · Cited by 562 · see citing works
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 · see citing works
Self-citationAmino acids and mTORC1: from lysosomes to disease
Efeyan, A., Zoncu, R., & Sabatini, D. M. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.05.007 · Cited by 436 · see citing works
Chen, D. L., Love, K. T., Chen, Y., Eltoukhy, A. A., Kastrup, C. J., Sahay, G., Jeon, A., Dong, Y., Whitehead, K. A., & Anderson, D. G. (2012) · Journal of the American Chemical Society · doi:10.1021/ja301621z · Cited by 422 · see citing works
Self-citationFenton, O. S., Kauffman, K. J., Kaczmarek, J. C., McClellan, R. L., Jhunjhunwala, S., Tibbitt, M. W., Zeng, M. D., Appel, E. A., Dorkin, J. R., Mir, F. F., et al. (2017) · Advanced Materials · doi:10.1002/adma.201606944 · Cited by 289 · see citing works
Real-time multiple-particle tracking: applications to drug and gene delivery
Suh, J., Dawson, M., & Hanes, J. S. (2004) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2004.06.001 · Cited by 274 · see citing works
The lysosome as a command-and-control center for cellular metabolism
Lim, C.-Y., & Zoncu, R. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201607005 · Cited by 274 · see citing works
Exploiting Endocytosis for NanomedicinesPreprint
Akinc, A., & Battaglia, G. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016980 · Cited by 211 · see citing works
ER–endosome contact sites: molecular compositions and functions
Raiborg, C., Wenzel, E. M., & Stenmark, H. (2015) · The EMBO Journal · doi:10.15252/embj.201591481 · Cited by 191 · see citing works
Lipid Sorting and Multivesicular Endosome BiogenesisPreprint
Bissig, C., & Gruenberg, J. E. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016816 · Cited by 162 · see citing works
Lipid-mediated delivery of RNA is more efficient than delivery of DNA in non-dividing cells
Zou, S., Scarfo, K. A., Nantz, M. H., & Hecker, J. G. (2010) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2010.01.019 · Cited by 161 · 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
The Late Endosome is Essential for mTORC1 Signaling
Flinn, R. J., Yan, Y., Goswami, S., Parker, P. J., & Backer, J. (2010) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-09-0756 · Cited by 158 · see citing works
Challenges in carrier‐mediated intracellular delivery: moving beyond endosomal barriers
Stewart, M. P., Lorenz, A. S., Dahlman, J. E., & Sahay, G. (2015) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1377 · Cited by 154 · see citing works
Self-citationCuboplexes: Topologically Active siRNA Delivery
Kim, H., & Leal, C. (2015) · ACS Nano · doi:10.1021/acsnano.5b03902 · Cited by 153 · see citing works
Antileukotriene Drugs: Clinical Application, Effectiveness and Safety
Riccioni, G., Bucciarelli, T., Mancini, B., et al. (2007) · Current Medicinal Chemistry · doi:10.2174/092986707781368522 · Cited by 125 · see citing works
Youn, H., & Chung, J.-K. (2015) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2015.1057563 · Cited by 114 · see citing works
Myocardial Delivery of Lipidoid Nanoparticle Carrying modRNA Induces Rapid and Transient Expression
Turnbull, I. C., Eltoukhy, A. A., Fish, K. M., Nonnenmacher, M. E., Ishikawa, K., Chen, J., Hajjar, R. J., Anderson, D. G., & Costa, K. D. (2015) · Molecular Therapy · doi:10.1038/mt.2015.193 · Cited by 112 · see citing works
Yang, B., Ming, X., Cao, C., Laing, B. M., Yuan, A., Porter, M. A., Hull-Ryde, E. A., Maddry, J. A., Suto, M. J., Janzen, W. P., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv060 · Cited by 94 · see citing works
Screening of mRNA Chemical Modification to Maximize Protein Expression with Reduced Immunogenicity
Uchida, S., Kataoka, K., & Itaka, K. (2015) · Pharmaceutics · doi:10.3390/pharmaceutics7030137 · Cited by 88 · see citing works
Identification of siRNA delivery enhancers by a chemical library screen
Gilleron, J., Paramasivam, P., Zeigerer, A., Querbes, W., Marsico, G., Andree, C., Seifert, S., Amaya, P., Stöter, M., Koteliansky, V., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv762 · Cited by 69 · see citing works
Seiffert, M., Stilgenbauer, S., Döhner, H., et al. (2007) · Leukemia · doi:10.1038/sj.leu.2404863 · Cited by 68 · see citing works
Wang, Y., & Huang, L. (2013) · Nature Biotechnology · doi:10.1038/nbt.2634 · Cited by 62 · see citing works
RNActive® Technology: Generation and Testing of Stable and Immunogenic mRNA Vaccines
Rauch, S., Lutz, J., Kowalczyk, A., Schlake, T., & Heidenreich, R. (2017) · Methods in Molecular Biology · doi:10.1007/978-1-4939-6481-9_5 · Cited by 57 · see citing works
Niemann-Pick C1 Functions in Regulating Lysosomal Amine Content
Kaufmann, A. M., & Krise, J. P. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803715200 · Cited by 53 · see citing works
Peterson, B. G., Tan, K. W., Osa-Andrews, B., & Iram, S. H. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.02.024 · Cited by 49 · see citing works
Liu, Y., Khawaja, A. M., & Rogers, D. F. (1998) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701886 · Cited by 46 · see citing works
Studying Lipids Involved in the Endosomal Pathway
Bissig, C., Johnson, S., & Gruenberg, J. E. (2012) · Methods in cell biology · doi:10.1016/b978-0-12-386487-1.00002-x · Cited by 21 · see citing works
Chen, H., Yang, H., Wang, Z., et al. (2016) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.5b00482 · Cited by 14 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- [22]Yin H Kanasty RL Eltoukhy AA Vegas AJ Dorkin JR Anderson DG Nat Rev Genet 2014 15 8 541 555 25022906
- [27]Semple SC Akinc A Chen J Sandhu AP Mui BL Cho CK Sah DWY Stebbing D Crosley EJ Yaworski E Hafez IM Dorkin JR Qin J Lam K Rajeev KG Wong KF Jeffs LB Nechev L Eisenhardt ML Jayaraman M Kazem M Maier MA Srinivasulu M Weinstein MJ Chen Q Alvarez R Barros SA De S Klimuk SK Borland T Kosovrasti V Cantley WL Tam YK Manoharan M Ciufolini MA Tracy MA de Fougerolles A MacLachlan I Cullis PR Madden TD Hope MJ Nat Biotechnol 2010 28 2 172 176 20081866
- [51]Gilleron J Querbes W Zeigerer A Borodovsky A Marsico G Schubert U Manygoats K Seifert S Andree C Stöter M Epstein-Barash H Zhang L Koteliansky V Fitzgerald K Fava E Bickle M Kalaidzidis Y Akinc A Maier M Zerial M Nat Biotechnol 2013 31 7 638 646 23792630
- [52]Sahay G Querbes W Alabi C Eltoukhy A Sarkar S Zurenko C Karagiannis E Love K Chen D Zoncu R Buganim Y Schroeder A Langer R Anderson DG Nat Biotechnol 2013 31 7 653 658 23792629 PMC3814166
Cited by
Sorted by citations
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
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
Self-citationIonizable Lipid Nanoparticle-Mediated mRNA Delivery for Human CAR T Cell Engineering
Billingsley, M. M., Singh, N., Ravikumar, P., Zhang, R., June, C. H., & Mitchell, M. J. (2020) · Nano Letters · doi:10.1021/acs.nanolett.9b04246 · Cited by 636 · 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
Addressing the Cold Reality of mRNA Vaccine Stability
Crommelin, D. J. A., Anchordoquy, T. J., Volkin, D. B., Jiskoot, W., & Mastrobattista, E. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2020.12.006 · Cited by 517 · see citing works
Yanez Arteta, M., Kjellman, T., Bartesaghi, S., Wallin, S., Wu, X., Kvist, A. J., Dabkowska, A., Székely, N., Radulescu, A., Bergenholtz, J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1720542115 · Cited by 534 · see citing works
mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases
Maruggi, G., Zhang, C., Li, J., Ulmer, J. B., & Yu, D. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.01.020 · Cited by 507 · 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
Linkage between endosomal escape of LNP-mRNA and loading into EVs for transport to other cells
Maugeri, M., Nawaz, M., Papadimitriou, A., Angerfors, A., Camponeschi, A., Na, M., Hölttä, M., Skantze, P., Johansson, S., Sundqvist, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12275-6 · Cited by 428 · 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
Impact of mRNA chemistry and manufacturing process on innate immune activation
Nelson, J., Sorensen, E. W., Mintri, S., Rabideau, A. E., Zheng, W., Besin, G., Khatwani, N., Su, S. V., Miracco, E. J., Issa, W. J., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaz6893 · Cited by 354 · see citing works
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 · see citing works
Hajj, K. A., Ball, R. L., Deluty, S. B., Singh, S. R., Strelkova, D., Knapp, C. M., & Whitehead, K. A. (2019) · Small · doi:10.1002/smll.201805097 · Cited by 312 · see citing works
Lipid Nanoparticle-Delivered Chemically Modified mRNA Restores Chloride Secretion in Cystic Fibrosis
Robinson, E., MacDonald, K. D., Slaughter, K., McKinney, M., Patel, S., Sun, C., & Sahay, G. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.05.014 · Cited by 272 · see citing works
Self-citationLipid 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
Self-citationCheng, 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
The effects of PEGylation on LNP based mRNA delivery to the eye
Ryals, R. C., Patel, S., Acosta, C., McKinney, M., Pennesi, M. E., & Sahay, G. (2020) · PLOS ONE · doi:10.1371/journal.pone.0241006 · Cited by 194 · see citing works
Self-citationLoughrey, D., & Dahlman, J. E. (2022) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00601 · Cited by 173 · see citing works
Nanoscale 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
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
Mild Innate Immune Activation Overrides Efficient Nanoparticle‐Mediated RNA Delivery
Lokugamage, M. P., Gan, Z., Zurla, C., Levin, J., Islam, F. Z., Kalathoor, S., Sato, M., Sago, C. D., Santangelo, P. J., & Dahlman, J. E. (2020) · Advanced Materials · doi:10.1002/adma.201904905 · 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
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
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
Self-citationZhu, Y., Meng, T., Tan, Y., Yang, X., Liu, Y., Liu, X., Yu, F., Wen, L., Dai, S., Yuan, H., et al. (2018) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.8b00842 · Cited by 42 · see citing works
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
The Daunting Economics of Therapeutic Genome Editing
Wilson, R. C., & Carroll, D. (2019) · The CRISPR Journal · doi:10.1089/crispr.2019.0052 · Cited by 33 · see citing works
Legere, R. M., Cohen, N. D., Poveda, C., Bray, J. M., Barhoumi, R., Szule, J. A., de la Concha-Bermejillo, A., Bordin, A. I., & Pollet, J. (2021) · Scientific Reports · doi:10.1038/s41598-020-79855-1 · Cited by 20 · see citing works
Matrix stiffness regulates lipid nanoparticle-mRNA delivery in cell-laden hydrogels
Athirasala, A., Patel, S., Menezes, P. P., Kim, J., Tahayeri, A., Sahay, G., & Bertassoni, L. E. (2022) · Nanomedicine: Nanotechnology, Biology and Medicine · doi:10.1016/j.nano.2022.102550 · Cited by 16 · see citing works
Self-citation
- Authors
- Patel, S., Ashwanikumar, N., Robinson, E., DuRoss, A., Sun, C., Murphy-Benenato, K. E., Mihai, C., Almarsson, Ö., & Sahay, G.
- Affiliations
- Oregon State University (US)
- Moderna Therapeutics (United States) (US)
- Corresponding author
- Sahay, Gaurav
- Venue
- Nano Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-08-24
- Volume
- 17
- Issue
- 9
- Pages
- 5711-5718
- ISSN
- 1530-6984 (ISSN-L)
- 1530-6992
- PMC
- PMC5623340
- OpenAlex
- W2748490245
- Cited by
- 251
- References
- 56
- Citations by year
- 2026: 27 · 2025: 29 · 2024: 30 · 2023: 27 · 2022: 29 · 2021: 38 · 2020: 30 · 2019: 22 · 2018: 19
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nano Letters (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Biomedical Imaging and Bioengineering (1R15EB021581-01)
- Cystic Fibrosis Foundation
- Moderna Therapeutics
- College of Pharmacy, Ohio State University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- lipid nanoparticles, mRNA delivery, endosomal escape, lysosome formation, late endosomes, mTOR signaling, leukotriene antagonists, RNA therapeutics, vaccine delivery
- MeSH terms
- Animals, Cell Line, Female, HeLa Cells, Humans, Lipids, Lysosomes, Mice, Inbred BALB C, Endosomes, RNA, Messenger, Signal Transduction, Gene Transfer Techniques, Lipid Metabolism, Nanoparticles, Hep G2 Cells, TOR Serine-Threonine Kinases
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
