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Nanoparticles Containing Oxidized Cholesterol Deliver mRNA to the Liver Microenvironment at Clinically Relevant Doses
Open accessAbstract
Using mRNA to produce therapeutic proteins is a promising approach to treat genetic diseases. However, systemically delivering mRNA to cell types besides hepatocytes remains challenging. Fast identification of nanoparticle delivery (FIND) is a DNA barcode‐based system designed to measure how over 100 lipid nanoparticles (LNPs) deliver mRNA that functions in the cytoplasm of target cells in a single mouse. By using FIND to quantify how 75 chemically distinct LNPs delivered mRNA to 28 cell types in vivo, it is found that an LNP formulated with oxidized cholesterol and no targeting ligand delivers Cre mRNA, which edits DNA in hepatic endothelial cells and Kupffer cells at 0.05 mg kg−1. Notably, the LNP targets liver microenvironmental cells fivefold more potently than hepatocytes. The structure of the oxidized cholesterols added to the LNP is systematically varied to show that the position of the oxidative modification may be important; cholesterols modified on the hydrocarbon tail associated with sterol ring D tend to outperform cholesterols modified on sterol ring B. These data suggest that LNPs formulated with modified cholesterols can deliver gene‐editing mRNA to the liver microenvironment at clinically relevant doses.
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“For example, barcoding has been applied to study how the structure of cholesterol derivatives impact cell selectivity of lipid nanoparticles, revealing that selective accumulation in liver endothelial cells, Kupffer cells and hepatocytes125,126 depends on cholesterol structures.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [126]
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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
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
Cellular cholesterol trafficking and compartmentalization
Ikonen, E. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2336 · Cited by 1,506
Liver sinusoidal endothelial cells: Physiology and role in liver diseases
Poisson, J., Lemoinne, S., Boulanger, C., Durand, F., Moreau, R., Valla, D., & Rautou, P.-E. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2016.07.009 · Cited by 1,047
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
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
Miller, J. B., Zhang, S., Kos, P., Xiong, H., Zhou, K., Perelman, S. S., Zhu, H., & Siegwart, D. J. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201610209 · Cited by 540
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
Role of Kupffer cells in the pathogenesis of liver disease
Kolios, G. (2006) · World Journal of Gastroenterology · doi:10.3748/wjg.v12.i46.7413 · Cited by 505
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
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Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076
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
Drug delivery systems for RNA therapeutics
Paunovska, K., Loughrey, D., & Dahlman, J. E. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00439-4 · Cited by 1,349
Self-citationChemistry of Lipid Nanoparticles for RNA Delivery
Eygeris, Y., Gupta, M., Kim, J., & Sahay, G. (2021) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00544 · Cited by 917
Engineered biomaterials for in situ tissue regeneration
Gaharwar, A. K., Singh, I., & Khademhosseini, A. (2020) · Nature Reviews Materials · doi:10.1038/s41578-020-0209-x · Cited by 892
mRNA-based therapeutics: powerful and versatile tools to combat diseases
Qin, S., Tang, X., Chen, Y., Chen, K., Fan, N., Xiao, W., Zheng, Q., Li, G., Teng, Y., Wu, M., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01007-w · Cited by 852
“Nanoparticles containing cKK-E12 and nine different cholesterol variants were prepared for delivering mRNA, and the results revealed that the oxidative position of cholesterol influences nanoparticle targeting by adsorbing different protein coronas onto LNPs and that nanoparticles including 20α-OH cholesterol can targ…”
Dilliard, S. A., & Siegwart, D. J. (2023) · Nature Reviews Materials · doi:10.1038/s41578-022-00529-7 · Cited by 744
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
Lipids and Lipid Derivatives for RNA Delivery
Zhang, Y., Sun, C., Wang, C., Jankovic, K. E., & Dong, Y. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00244 · Cited by 649
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
“A previous study showed that LNPs made from oxidatively modified cholesterol can deliver mRNA to the liver microenvironment in a targeted manner.(303) The PEGylated lipid is the least abundant component in LNPs formulation and is composed of hydrophilic polyethylene glycol (PEG) and a hydrophobic anchoring lipid [dimy…”
BackgroundPatel, 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
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
The landscape of mRNA nanomedicine
Huang, X., Kong, N., Zhang, X., Cao, Y., Langer, R., & Tao, W. (2022) · Nature Medicine · doi:10.1038/s41591-022-02061-1 · Cited by 511
Optimization of lipid nanoparticles for the delivery of nebulized therapeutic mRNA to the lungs
Lokugamage, M. P., Vanover, D. A., Beyersdorf, J. P., Hatit, M. Z. C., Rotolo, L., Echeverri, E. S., Peck, H. E., Ni, H., Yoon, J., Kim, Y., et al. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00786-x · Cited by 539
Self-citationmRNA-based cancer therapeutics
Liu, C., Shi, Q., Huang, X., Koo, S., Kong, N., & Tao, W. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-023-00586-2 · Cited by 500
Lipid Nanoparticle (LNP) Enables mRNA Delivery for Cancer Therapy
Zong, Y., Lin, Y., Wei, T., & Cheng, Q. (2023) · Advanced Materials · doi:10.1002/adma.202303261 · Cited by 506
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
“The hydrophobic tail, sterol ring flexibility, and polarity of hydroxy groups in cholesterol was reported to impact the efficacy of LNP delivery [74].”
BackgroundThe 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
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
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
Targeting cancer with mRNA–lipid nanoparticles: key considerations and future prospects
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
“Efforts to optimize formulations for endogenous targeting of different tissues focus on both in vitro and in vivo screens that commonly use reporters for LNP biodistribution, the most common of which are DNA barcodes 29,47–49 .”
BackgroundKumar, S., Duan, Q., Wu, R., Harris, E. N., & Su, Q. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113869 · Cited by 382
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
LoPresti, S. T., Arral, M. L., Chaudhary, N., & Whitehead, K. A. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.03.046 · Cited by 293
Engineering Lipid Nanoparticles for Enhanced Intracellular Delivery of mRNA through Inhalation
Kim, J., Jozić, A., Lin, Y., Eygeris, Y., Bloom, E., Tan, X., Acosta, C., MacDonald, K. D., Welsher, K., & Sahay, G. (2022) · ACS Nano · doi:10.1021/acsnano.2c05647 · Cited by 292
Reformulating lipid nanoparticles for organ-targeted mRNA accumulation and translation
Su, K., Shi, L., Sheng, T., Yan, X., Lin, L., Meng, C., Wu, S., Chen, Y., Zhang, Y., Wang, C., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50093-7 · Cited by 292
“Numerous prior efforts have focused on functionalizing cholesterol through chemical modi fi cations or charge variations, enabling enhancement of mRNA-LNP delivery ef fi cacy and accomplishment of extrahepatic mRNA expression 44,51 – 54 .”
Strategies to reduce the risks of mRNA drug and vaccine toxicity
Bitounis, D., Jacquinet, E., Rogers, M. A., & Amiji, M. M. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00859-3 · Cited by 242
“…58 , PEGylated lipids improve aqueous colloidal stability and impede LNP uptake by the mononuclear phagocyte system (MPS) 59 , cholesterol imparts flexibility and allows fusion with cellular membranes 60 , and helper lipids provide structural integrity and improve encapsulation efficiency 61,62 .”
Álvarez‐Benedicto, E., Farbiak, L., Ramírez, M. M., Wang, X., Johnson, L. T., Mian, O. T., Guerrero, E. D., & Siegwart, D. J. (2021) · Biomaterials Science · doi:10.1039/d1bm01454d · Cited by 235
Ionizable lipid nanoparticles encapsulating barcoded mRNA for accelerated in vivo delivery screening
Guimarães, P. P. G., Zhang, R., Spektor, R., Tan, M., Chung, A., Billingsley, M. M., El-Mayta, R. D., Riley, R., Wang, L., Wilson, J. M., et al. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.10.028 · Cited by 224
Jeong, M., Lee, Y., Park, J., Jung, H., & Lee, H. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114990 · Cited by 232
Anionic Lipid Nanoparticles Preferentially Deliver mRNA to the Hepatic Reticuloendothelial System
Pattipeiluhu, R., Arias‐Alpizar, G., Basha, G., Chan, K. Y. T., Bussmann, J., Sharp, T. H., Moradi, M., Sommerdijk, N., Harris, E. N., Cullis, P. R., et al. (2022) · Advanced Materials · doi:10.1002/adma.202201095 · Cited by 194
Piperazine-derived lipid nanoparticles deliver mRNA to immune cells in vivo
Ni, H., Hatit, M. Z. C., Zhao, K., Loughrey, D., Lokugamage, M. P., Peck, H. E., Cid, A. D., Muralidharan, A., Kim, Y., Santangelo, P. J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32281-5 · Cited by 202
Self-citationHosseini-Kharat, M., Bremmell, K. E., & Prestidge, C. A. (2025) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2025.101436 · Cited by 215
Nucleic acid drugs: recent progress and future perspectives
Sun, X., Setrerrahmane, S., Li, C., Hu, J., & Xu, H. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02035-4 · Cited by 225
Drug delivery systems for CRISPR-based genome editors
Madigan, V. J., Zhang, F., & Dahlman, J. E. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00762-x · Cited by 193
Self-citationLoughrey, D., & Dahlman, J. E. (2022) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00601 · Cited by 173
Self-citationLi, J., Chen, C., & Xia, T. (2022) · Advanced Materials · doi:10.1002/adma.202106456 · Cited by 172
Munson, M. J., O’Driscoll, G., da Silva, A. M., Lázaro‐Ibáñez, E., Gallud, A., Wilson, J. T., Collén, A., Esbjörner, E. K., & Sabirsh, A. (2021) · Communications Biology · doi:10.1038/s42003-021-01728-8 · Cited by 160
Strategies for non-viral vectors targeting organs beyond the liver
Kim, J., Eygeris, Y., Ryals, R. C., Jozić, A., & Sahay, G. (2023) · Nature Nanotechnology · doi:10.1038/s41565-023-01563-4 · Cited by 160
“Lastly, although Kupffer cells currently attract little attention as a gene therapy target, incorporation of oxidized cholesterol derivatives in LNPs has been shown to enhance Kupffer cell transfection in mice 21 .”
Species-dependent in vivo mRNA delivery and cellular responses to nanoparticles
Hatit, M. Z. C., Lokugamage, M. P., Dobrowolski, C. N., Paunovska, K., Ni, H., Zhao, K., Vanover, D. A., Beyersdorf, J. P., Peck, H. E., Loughrey, D., et al. (2022) · Nature Nanotechnology · doi:10.1038/s41565-021-01030-y · Cited by 158
Self-citationmRNA in the Context of Protein Replacement Therapy
Vavilis, T., Stamoula, Ε., Ainatzoglou, A., Sachinidis, A., Lamprinou, M., Dardalas, I., & Vizirianakis, I. S. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15010166 · Cited by 145
Lipid Nanoparticles Optimized for Targeting and Release of Nucleic Acid
Jia, Y., Wang, X., Li, L., Li, F., Zhang, J., & Liang, X. (2023) · Advanced Materials · doi:10.1002/adma.202305300 · Cited by 147
Physiological Barriers and Strategies of Lipid‐Based Nanoparticles for Nucleic Acid Drug Delivery
Hu, M., Li, X., You, Z., Cai, R., & Chen, C. (2023) · Advanced Materials · doi:10.1002/adma.202303266 · Cited by 142
Enhancing RNA-lipid nanoparticle delivery: Organ- and cell-specificity and barcoding strategies
Wei, P.-S., Thota, N., John, G., Chang, E., Lee, S., Wang, Y., Ma, Z., Tsai, Y.-H., & Mei, K. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.08.030 · Cited by 138
Understanding nanoparticle-liver interactions in nanomedicine
He, Y., Wang, Y., Wang, L., Jiang, W., & Wilhelm, S. (2024) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2024.2375400 · Cited by 145
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
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
Self-citationLi, G., Chen, T., Dahlman, J. E., Eniola‐Adefeso, L., Ghiran, I. C., Kurre, P., Lam, W. A., Lang, J. K., Marbán, E., Martı́n, P., et al. (2023) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12305 · Cited by 124
“…led to identification of several LNPs that specifically deliver functional cargo into splenic endothelial cells (Sago et al., 2018), hepatic endothelial cells (Paunovska et al., 2019), Kupffer cells (Paunovska et al., 2019) and lung endothelial cells (unpublished) following systemic administration.”
BackgroundSelf-citationPrecision medicine: In vivo CAR therapy as a showcase for receptor-targeted vector platforms
Michels, A., Ho, N., & Buchholz, C. J. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.05.018 · Cited by 131
Nakamura, T., Sato, Y., Yamada, Y., Abd Elwakil, M. M., Kimura, S., Younis, M. A., & Harashima, H. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114417 · Cited by 121
From structural design to delivery: mRNA therapeutics for cancer immunotherapy
Zhou, F., Huang, L., Li, S., Yang, W., Chen, F., Cai, Z., Liu, X., Xu, W., Lehto, V., Lächelt, U., et al. (2023) · Exploration · doi:10.1002/exp.20210146 · Cited by 117
The Future of Tissue-Targeted Lipid Nanoparticle-Mediated Nucleic Acid Delivery
Kularatne, R. N., Crist, R. M., & Stern, S. T. (2022) · Pharmaceuticals · doi:10.3390/ph15070897 · Cited by 109
“Cre mRNA * 5–8-week-old (sex not specified) Ai14 Lox-Stop-Lox-tdTomato and C57BL/6J mice hepatic endothelial and Kupffer cells [30]”
BackgroundMukai, H., Ogawa, K., Kato, N., & Kawakami, S. (2022) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2022.100450 · Cited by 108
“evaluation of not only mRNA delivery, but also of foreign protein expression was reported [71].”
BackgroundRecent advances in nanoparticulate RNA delivery systems
Witten, J. J., Hu, Y., Langer, R., & Anderson, D. G. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2307798120 · Cited by 113
Dobrowolski, C. N., Paunovska, K., Echeverri, E. S., Loughrey, D., Sanchez, A. J. D. S., Ni, H., Hatit, M. Z. C., Lokugamage, M. P., Kuzminich, Y., Peck, H. E., et al. (2022) · Nature Nanotechnology · doi:10.1038/s41565-022-01146-9 · Cited by 113
Self-citationRecent Advances in Site-Specific Lipid Nanoparticles for mRNA Delivery
Xu, X., & Xia, T. (2023) · ACS Nanoscience Au · doi:10.1021/acsnanoscienceau.2c00062 · Cited by 106
Simonsen, J. B. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.04.022 · Cited by 115
Lipid nanoparticles: Composition, formulation, and application
Xu, S., Hu, Z., Song, F., Xu, Y. G., & Han, X. (2025) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2025.101463 · Cited by 115
“56 Patel et al. found that the use of β -sitos- terol in enhanced LNP (eLNP) improved mRNA transfection ability.”
Haghighi, E., Abolmaali, S. S., Dehshahri, A., Shaegh, S. A. M., Azarpira, N., & Tamaddon, A. M. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02972-w · Cited by 125
‘Passive’ nanoparticles for organ-selective systemic delivery: design, mechanism and perspective
Fu, L., Zhang, Y., Farokhzad, R. A., Mendes, B. B., Conde, J., & Shi, J. (2023) · Chemical Society Reviews · doi:10.1039/d2cs00998f · Cited by 100
Lipid nanoparticle chemistry determines how nucleoside base modifications alter mRNA delivery
Melamed, J. R., Hajj, K. A., Chaudhary, N., Strelkova, D., Arral, M. L., Pardi, N., Alameh, M., Miller, J. B., Farbiak, L., Siegwart, D. J., et al. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.11.022 · Cited by 101
Lipid nanoparticle-based mRNA delivery systems for cancer immunotherapy
Han, J., Lim, J., Wang, C. J., Han, J., Shin, H. E., Kim, S.-N., Jeong, D., Lee, S. H., Chun, B.-H., Park, C. G., et al. (2023) · Nano Convergence · doi:10.1186/s40580-023-00385-3 · Cited by 100
Development of mRNA Lipid Nanoparticles: Targeting and Therapeutic Aspects
Liu, Y., Huang, Y., He, G., Guo, C., Dong, J., & Wu, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251810166 · Cited by 100
“Paunovska et al. [61] explored the use of different types of cholesterol to modify LNPs and reported that the structure of the cholesterol significantly affects the targeting ability of the LNPs.”
BackgroundXiong, H., Liu, S., Wei, T., Cheng, Q., & Siegwart, D. J. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.06.030 · Cited by 92
mRNA nanodelivery systems: targeting strategies and administration routes
Yuan, M., Han, Z., Liang, Y., Sun, Y., He, B., Chen, W., & Fan, L. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00425-3 · Cited by 98
“Further, higher mRNA expression could be selectively induced in hepatocytes, LSECs, and Kupffer cells by rationally changing the structure of oxidized cholesterol [110].”
BackgroundsiRNA Functionalized Lipid Nanoparticles (LNPs) in Management of Diseases
Kalita, T., Dezfouli, S. A., Pandey, L. M., & Uludağ, H. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14112520 · Cited by 90
Optimizing synthetic nucleic acid and protein nanocarriers: The chemical evolution approach
Freitag, F., & Wagner, E. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.03.005 · Cited by 83
Cationic cholesterol-dependent LNP delivery to lung stem cells, the liver, and heart
Radmand, A., Kim, H., Beyersdorf, J. P., Dobrowolski, C. N., Zenhausern, R., Paunovska, K., Huayamares, S. G., Hua, X., Han, K., Loughrey, D., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2307801120 · Cited by 84
“However, other observations suggest that LNP tropism can be complex, including data that cholesterol structure can influence delivery potentially by influencing endocytosis (21–23).”
BackgroundSelf-citationKawaguchi, M., Noda, M., Ono, A., Kamiya, M., Matsumoto, M., Tsurumaru, M., Mizukami, S., Mukai, H., & Kawakami, S. (2022) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2022.12.026 · Cited by 83
Gan, Z., Lokugamage, M. P., Hatit, M. Z. C., Loughrey, D., Paunovska, K., Sato, M., Cristian, A., & Dahlman, J. E. (2020) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10161 · Cited by 75
“We subsequently calculated the enrichment of different nanoparticle properties.(18) Briefly, we calculated how often a property would appear in particles that performed in the top 10% and particles that performed in the bottom 10%.”
Self-citationProtein and mRNA Delivery Enabled by Cholesteryl‐Based Biodegradable Lipidoid Nanoparticles
Li, Y., Jarvis, R., Zhu, K., Glass, Z., Ogurlu, R., Gao, P., Li, P., Chen, J., Yu, Y., Yang, Y., et al. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202004994 · Cited by 75
The Transcriptional Response to Lung-Targeting Lipid Nanoparticles in Vivo
Radmand, A., Lokugamage, M. P., Kim, H., Dobrowolski, C. N., Zenhausern, R., Loughrey, D., Huayamares, S. G., Hatit, M. Z. C., Ni, H., Cid, A. D., et al. (2023) · Nano Letters · doi:10.1021/acs.nanolett.2c04479 · Cited by 77
Self-citationZhang, R., Shao, S., Piao, Y., Xiang, J., Wei, X., Zhang, Z., Zhou, Z., Tang, J., Qiu, N., Xu, X., et al. (2023) · Advanced Materials · doi:10.1002/adma.202303614 · Cited by 72
Nanoparticle stereochemistry-dependent endocytic processing improves in vivo mRNA delivery
Hatit, M. Z. C., Dobrowolski, C. N., Lokugamage, M. P., Loughrey, D., Ni, H., Zurla, C., Sanchez, A. J. D. S., Radmand, A., Huayamares, S. G., Zenhausern, R., et al. (2023) · Nature Chemistry · doi:10.1038/s41557-023-01138-9 · Cited by 71
Self-citationZhang, H., & Barz, M. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.02.055 · Cited by 80
Using Large Datasets to Understand Nanotechnology
Paunovska, K., Loughrey, D., Sago, C. D., Langer, R., & Dahlman, J. E. (2019) · Advanced Materials · doi:10.1002/adma.201902798 · Cited by 69
Self-citationTreating Cystic Fibrosis with mRNA and CRISPR
Sanchez, A. D. S., Paunovska, K., Cristian, A., & Dahlman, J. E. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.137 · Cited by 75
“In the case of systemic mRNA therapies, off-target cells are likely to include macrophages and Kupffer cells, 12 and, as a result, an mRNA therapy targeting a given gene may lead to signifi-cant off-target effects if that gene alters macrophage or Kupffer cell function.”
Self-citationStructure and Morphology of Lipid Nanoparticles for Nucleic Acid Drug Delivery: A Review
Udepurkar, A. P., Devos, C., Sagmeister, P., Destro, F., Inguva, P., Ahmadi, S., Boulais, É., Quan, Y., Braatz, R. D., & Myerson, A. S. (2025) · ACS Nano · doi:10.1021/acsnano.4c18274 · Cited by 74
Therapeutic RNA Delivery for COVID and Other Diseases
Dobrowolski, C. N., Paunovska, K., Hatit, M. Z. C., Lokugamage, M. P., & Dahlman, J. E. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202002022 · Cited by 62
Self-citationDelivery of mRNA for regulating functions of immune cells
Shi, J. Y., Huang, M., Lu, Z.-D., Du, X., Shen, S., Xu, C., & Wang, J. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.03.033 · Cited by 62
Composition of lipid nanoparticles for targeted delivery: application to mRNA therapeutics
Vasileva, O., Zaborova, O. V., Shmykov, B., Ivanov, R. A., & Reshetnikov, V. V. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1466337 · Cited by 72
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
mRNA therapies: Pioneering a new era in rare genetic disease treatment
Shen, G., Liu, J., Yang, H., Xie, N., & Yang, Y. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.03.056 · Cited by 62
Principles of lipid nanoparticle design for mRNA delivery
Zhang, Y., Zhang, X., Gao, Y., & Liu, S. (2024) · BMEMat · doi:10.1002/bmm2.12116 · Cited by 62
Lipid Nanoparticles for Nucleic Acid Delivery to Endothelial Cells
Liu, G. W., Guzman, E. B., Menon, N., & Langer, R. (2023) · Pharmaceutical Research · doi:10.1007/s11095-023-03471-7 · Cited by 58
“recently reported that replacement of unmodified cholesterol with oxidized cholesterol from the formulation of cKK-E12 nanoparticles produced a five-fold improvement in the delivery of mRNA to liver endothelial cells [185].”
BackgroundDevelopment and applications of mRNA treatment based on lipid nanoparticles
Wang, Z., Ma, W., Fu, X., Qi, Y., Zhao, Y., & Zhang, S. (2023) · Biotechnology Advances · doi:10.1016/j.biotechadv.2023.108130 · Cited by 57
Lipid Nanoparticles for Delivery of CRISPR Gene Editing Components
Wu, F., Li, N., Xiao, Y., Palanki, R., Yamagata, H. M., Mitchell, M. J., & Han, X. (2025) · Small Methods · doi:10.1002/smtd.202401632 · Cited by 64
Targeting strategies for mRNA delivery
Meyer, R. A., Neshat, S. Y., Green, J. J., Santos, J. L., & Tuesca, A. D. (2022) · Materials Today Advances · doi:10.1016/j.mtadv.2022.100240 · Cited by 55
Substituting racemic ionizable lipids with stereopure ionizable lipids can increase mRNA delivery
Sanchez, A. J. D. S., Zhao, K., Huayamares, S. G., Hatit, M. Z. C., Lokugamage, M. P., Loughrey, D., Dobrowolski, C. N., Wang, S., Kim, H., Paunovska, K., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.11.037 · Cited by 53
Self-citationChemistry, manufacturing and controls strategies for using novel excipients in lipid nanoparticles
O’Brien, M. N., Foley, D. A., Pak, R. H., Lewis, J. A., McKinney, E., Egan, P. M., Yerabolu, R., Dane, E. L., Dirat, O., Gorka, L. S., et al. (2025) · Nature Nanotechnology · doi:10.1038/s41565-024-01833-9 · Cited by 57
“In all three commercial LNP products, the neutral sterol cholesterol is used 17,21,23,62 ; however, alternative sterols are also under investigation 67,68 .”
Li, X., Li, J., Wei, J., Du, W., Su, C., Shen, X., Zhao, A., & Xu, M. (2025) · MedComm · doi:10.1002/mco2.70414 · Cited by 60
“They reported that oxidatively modified cholesterol efficiently delivers mRNAs to cells within the liver microenvironment [70].”
Modulating intracellular pathways to improve non-viral delivery of RNA therapeutics
de Vyver, T. V., Smedt, S. C. D., & Raemdonck, K. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114041 · Cited by 51
Zhou, Q., Liu, Q., Wang, Y., Chen, J., Schmid, O., Rehberg, M., & Yang, L. (2024) · Advanced Science · doi:10.1002/advs.202308659 · Cited by 51
Hua, X., Han, K., Mandracchia, B., Radmand, A., Liu, W., Kim, H., Zhou, Y., Ehrlich, S. M., Li, K., Zheng, C., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46250-7 · Cited by 51
“Three days after LNP administration, we used LFC to assess the expression of tdTomato in the liver, spleen, and lung after Cre mRNA delivery in Ai14 mice.”
MethodResultInfluentialSelf-citationLipid nanoparticles for RNA delivery: Self-assembling vs driven-assembling strategies
Nele, V., Campani, V., Moosavian, S. A., & Rosa, G. D. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115291 · Cited by 58
Cell Subtypes Within the Liver Microenvironment Differentially Interact with Lipid Nanoparticles
Sago, C. D., Krupczak, B. R., Lokugamage, M. P., Gan, Z., & Dahlman, J. E. (2019) · Cellular and Molecular Bioengineering · doi:10.1007/s12195-019-00573-4 · Cited by 53
Self-citationThe nanomedicine rush: New strategies for unmet medical needs based on innovative nano DDS
Sato, Y., Nakamura, T., Yamada, Y., & Harashima, H. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.12.032 · Cited by 50
Comprehensive analysis of lipid nanoparticle formulation and preparation for RNA delivery
Haque, M. A., Shrestha, A., Mikelis, C. M., & Mattheolabakis, G. (2024) · International Journal of Pharmaceutics X · doi:10.1016/j.ijpx.2024.100283 · Cited by 52
Cellular Trafficking of Nanotechnology‐Mediated mRNA Delivery
Huang, P., Deng, H., Wang, C., Zhou, Y., & Chen, X. S. (2023) · Advanced Materials · doi:10.1002/adma.202307822 · Cited by 53
Steering the course of CAR T cell therapy with lipid nanoparticles
Khawar, M. B., Afzal, A., Si, Y., & Sun, H. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02630-1 · Cited by 54
“They identified an LNP with oxidized cholesterol that efficiently delivered Cre mRNA to liver microenvironmental cells, showcasing the potential for gene editing in clinically relevant doses [100].”
Background
Metadata
- Authors
- Paunovska, K., Da Silva Sanchez, A. J., Sago, C. D., Gan, Z., Lokugamage, M. P., Islam, F. Z., Kalathoor, S., Krupczak, B. R., & Dahlman, J. E.
- Affiliations
- Georgia Institute of Technology (US)
- Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory School of Medicine Atlanta GA 30332 USA
- Corresponding author
- Dahlman, James E.
- ORCID
- Venue
- Advanced Materials
- Publisher
- Wiley
- Published
- 2019-02-12
- Volume
- 31
- Issue
- 14
- Pages
- e1807748-e1807748
- ISSN
- 0935-9648 (ISSN-L)
- 1521-4095
- PMC
- PMC6445717
- OpenAlex
- W2913721132
- Cited by
- 205
- References
- 26
- Citations by year
- 2026: 21 · 2025: 31 · 2024: 40 · 2023: 40 · 2022: 34 · 2021: 15 · 2020: 19 · 2019: 4
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Advanced Materials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM008433, T32GM105490)
- National Institute of Biomedical Imaging and Bioengineering (T32EB021962)
- 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 › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- lipid nanoparticles, oxysterols, mRNA delivery, liver microenvironment, genome editing, hepatic endothelial cells, Kupffer cells, nanoparticle targeting, in vivo delivery
- MeSH terms
- Animals, Cholesterol, Drug Carriers, Liver, Oxidation-Reduction, RNA, Messenger, Mice, Nanoparticles, Cellular Microenvironment
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