The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
A Novel Amino Lipid Series for mRNA Delivery: Improved Endosomal Escape and Sustained Pharmacology and Safety in Non-human Primates
Open accessAbstract
The success of mRNA-based therapies depends on the availability of a safe and efficient delivery vehicle. Lipid nanoparticles have been identified as a viable option. However, there are concerns whether an acceptable tolerability profile for chronic dosing can be achieved. The efficiency and tolerability of lipid nanoparticles has been attributed to the amino lipid. Therefore, we developed a new series of amino lipids that address this concern. Clear structure-activity relationships were developed that resulted in a new amino lipid that affords efficient mRNA delivery in rodent and primate models with optimal pharmacokinetics. A 1-month toxicology evaluation in rat and non-human primate demonstrated no adverse events with the new lipid nanoparticle system. Mechanistic studies demonstrate that the improved efficiency can be attributed to increased endosomal escape. This effort has resulted in the first example of the ability to safely repeat dose mRNA-containing lipid nanoparticles in non-human primate at therapeutically relevant levels.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Based on these observations, Moderna has developed an ionizable lipid (namely Lipid H, SM-102), whose tail adopts larger branches which in turn increases potency, and whose introduced ester bonds increase biodegradability (Fig. 7).290,291”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [290]
In the citing paper
“All three major players in the mRNA vaccine field have previously optimized so-called lipid nanoparticles (LNPs), constructs that typically consist of an ionizable lipid and one or more helper lipids to improve LNP stability and promote endosomal escape upon cellular uptake [12,13]”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [12]
In the citing paper
“the usage of the SM-102 lipid in Moderna's mRNA-1273 vaccine was found to outperform Onpattro's MC3 LNPs for the intramuscular (i.m.) delivery of mRNA in rodents and non-human primates, given its improved tolerability and higher endosomal escape efficiency [12,13]”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [12]
In the citing paper
“Endosomal escape can be increased by optimizing the pKa values of ionizable lipids66,76–78,88,100,140.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [77]
In the citing paper
“To improve the biocompatibility of lipid nanoparticles, biodegradable lipids can be applied76–78,108,179.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [77]
In the citing paper
“Moreover, the delivery efficacy of mRNA could be improved, for example, by rational design of lipids through modulation of head groups and hydrophobic tails to increase cellular uptake and endosomal escape of lipid nanoparticle–mRNA formulations64,66,76–78,88,97,100,114,140,141.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [77]
Citations
Cites
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
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
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
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
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
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
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
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
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
Self-citationMaier, 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
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–200 of 820
Liu, S., Wen, Y., Shan, X., Ma, X., Yang, C., Cheng, X., Zhao, Y., Li, J., Mi, S., Huo, H., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53914-x · Cited by 168
“29 and 30).”
InfluentialEnhancing immunotherapy with tumour-responsive nanomaterials
Linderman, S. W., DeRidder, L. B., Sanjurjo, L., Foote, M. B., Alonso, M. J., Kirtane, A. R., Langer, R., & Traverso, G. (2025) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-025-01000-6 · Cited by 165
“This nanoparticle platform features a modified amino-lipid tail providing improved particle stability, cellular fusogenic potential and an ability to escape from intracellular vesicles 105 .”
Mrksich, K., Padilla, M. S., & Mitchell, M. J. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115446 · Cited by 162
Nanomedicine-Based Approaches for mRNA Delivery
Uchida, S., Perche, F., Pichon, C., & Cabral, H. (2020) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00618 · Cited by 139
Rhym, L. H., Manan, R. S., Koller, A. A., Stephanie, G., & Anderson, D. G. (2023) · Nature Biomedical Engineering · doi:10.1038/s41551-023-01030-4 · Cited by 137
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
Current Status and Future Perspectives on MRNA Drug Manufacturing
Webb, C., Ip, S. Y., Bathula, N. V., Popova, P. G., Soriano, S. K. V., Ly, B.-H., Eryilmaz, B., Huu, V. A. N., Broadhead, R., Rabel, M., et al. (2022) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.2c00010 · Cited by 134
The immunostimulatory nature of mRNA lipid nanoparticles
Sharma, P., Hoorn, D., Aitha, A., Breier, D., & Peer, D. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115175 · Cited by 132
mRNA as novel technology for passive immunotherapy
Schlake, T., Theß, A., Thran, M., & Jordan, I. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2935-4 · Cited by 135
“presented expression results in NHPs using a proprietary LNP formulation [269] .”
BackgroundMethodInfluentialEscaping the endosome: assessing cellular trafficking mechanisms of non-viral vehicles
Xu, E., Saltzman, W. M., & Piotrowski-Daspit, A. S. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.05.038 · Cited by 139
Lipid carriers for mRNA delivery
Zhang, W., Jiang, Y., He, Y., Boucetta, H., Wu, J., Chen, Z., & He, W. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.11.026 · Cited by 134
“By optimizing the lipid tail and introducing a primary lipid (similar to that observed with an MC3-based series), Sabnis et al. 90 present amino lipids with good pharmacokinetics.”
Amplifying gene expression with RNA-targeted therapeutics
Khorkova, O., Stahl, J., Joji, A., Volmar, C., & Wahlestedt, C. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00704-7 · Cited by 136
Nanoplatforms for mRNA Therapeutics
Meng, C., Chen, Z., Li, G., Welte, T., & Shen, H. (2021) · Advanced Therapeutics · doi:10.1002/adtp.202000099 · Cited by 130
Cornebise, M., Narayanan, E., Xia, Y., Acosta, E. P., Ci, L., Koch, H., Milton, J., Sabnis, S., Salerno, T., & Benenato, K. E. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202106727 · Cited by 134
Self-citationEnhancing 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
Phosphatidylserine Lipid Nanoparticles Promote Systemic RNA Delivery to Secondary Lymphoid Organs
Luozhong, S., Yuan, Z., Sarmiento, T., Chen, Y., Gu, W., McCurdy, C., Gao, W., Li, R., Wilkens, S., & Jiang, S. (2022) · Nano Letters · doi:10.1021/acs.nanolett.2c03234 · Cited by 129
Iterative Design of Ionizable Lipids for Intramuscular mRNA Delivery
Tilstra, G., Couture‐Senécal, J., Lau, Y. M. A., Manning, A. M., Wong, D., Janaeska, W. W., Wuraola, T. A., Pang, J., & Khan, O. F. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.2c10670 · Cited by 132
Dual mRNA therapy restores metabolic function in long-term studies in mice with propionic acidemia
Jiang, L., Park, J.-S., Yin, L., Laureano, R., Jacquinet, E., Yang, J., Liang, S., Frassetto, A., Zhuo, J., Yan, X., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19156-3 · Cited by 129
Self-citationBiodegradable Cationic and Ionizable Cationic Lipids: A Roadmap for Safer Pharmaceutical Excipients
Jörgensen, A. M., Wibel, R., & Bernkop‐Schnürch, A. (2023) · Small · doi:10.1002/smll.202206968 · Cited by 131
Lipid polymer hybrid nanoparticles as potent vehicles for drug delivery in cancer therapeutics
Parveen, S., Gupta, P., Kumar, S., & Banerjee, M. (2023) · Medicine in Drug Discovery · doi:10.1016/j.medidd.2023.100165 · Cited by 131
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
Erasmus, J. H., Archer, J., Fuerte-Stone, J., Khandhar, A. P., Voigt, E., Granger, B., Bombardi, R. G., Govero, J., Tan, Q., Durnell, L. A., et al. (2020) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2020.06.011 · Cited by 118
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
Messenger RNA therapy for rare genetic metabolic diseases
Berraondo, P., Martini, P. G. V., Avila, M. A., & Fontanellas, A. (2019) · Gut · doi:10.1136/gutjnl-2019-318269 · Cited by 121
Targeted Delivery of mRNA with One-Component Ionizable Amphiphilic Janus Dendrimers
Zhang, D., Atochina‐Vasserman, E. N., Maurya, D. S., Liu, M., Xiao, Q., Lu, J., Lauri, G., Ona, N. A., Reagan, E. K., Ni, H., et al. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.1c09585 · Cited by 118
Sayers, E. J., Peel, S. E., Schantz, A., England, R., Beano, M., Bates, S. M., Desai, A. S., Puri, S., Ashford, M. B., & Jones, A. T. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.07.018 · Cited by 119
“EGFP mRNA (996 nucleotides) ARCA capped modified with 5-methylcytidine and pseudouridine used for in vitro work was purchased from TriLink Biotechnologies, while EGFP and luciferase mRNAs used in the cell screen and in vivo analysis were provided by Moderna.35 Citrate buffer was purchased from Teknova, and HyClone RNa…”
MethodInfluentialFrom 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
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
Lam, K., Leung, A., Martin, A., Wood, M., Schreiner, P., Palmer, L., Daly, O. M., Zhao, W., McClintock, K., & Heyes, J. A. (2023) · Advanced Materials · doi:10.1002/adma.202209624 · Cited by 118
mRNA delivery systems for cancer immunotherapy: Lipid nanoparticles and beyond
Sentí, M. E., del Valle, L. G., & Schiffelers, R. M. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115190 · Cited by 124
Quantitating Endosomal Escape of a Library of Polymers for mRNA Delivery
Jiang, Y., Qiao, L., Wang, Y., Xu, E., Ho, A. S. L., Singh, P., Wang, Y., Jiang, Z., Yang, F., Tietjen, G. T., et al. (2020) · Nano Letters · doi:10.1021/acs.nanolett.9b04426 · Cited by 111
Tse, S., McKinney, K. M., Walker, W., Nguyen, M., Iacovelli, J., Small, C. G., Hopson, K., Zaks, T. Z., & Huang, E. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.03.002 · Cited by 114
“The structure and composition of the LNP was similar to that described previously.(69) Formulations were tested for particle size, RNA encapsulation, and endotoxin.”
ResultZhang, D., Atochina‐Vasserman, E. N., Lu, J., Maurya, D. S., Xiao, Q., Liu, M., Adamson, J., Ona, N. A., Reagan, E. K., Ni, H., et al. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.2c00273 · Cited by 113
Non-immunotherapy application of LNP-mRNA: Maximizing efficacy and safety
Vlatkovic, I. (2021) · Biomedicines · doi:10.3390/biomedicines9050530 · Cited by 112
Besin, G., Milton, J., Sabnis, S., Howell, R. D., Mihai, C., Burke, K. E., Benenato, K. E., Stanton, M., Smith, P., Senn, J. J., et al. (2019) · ImmunoHorizons · doi:10.4049/immunohorizons.1900029 · Cited by 108
“Lipid nanoparticles LNP formulations were prepared using a modified procedure of a method previously described (14).”
MethodSelf-citationRecent 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
Chen, Z., Tian, Y., Yang, J., Wu, F., Liu, S., Cao, W., Xu, W., Hu, T., Siegwart, D. J., & Xiong, H. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c09143 · Cited by 108
Surface-Functionalized PEGylated Nanoparticles Deliver Messenger RNA to Pulmonary Immune Cells
Ke, X., Shelton, L., Hu, Y., Zhu, Y., Chow, E., Tang, H., Santos, J. L., & Mao, H. (2020) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.0c08268 · Cited by 102
Lipid Nanoparticle Technologies for Nucleic Acid Delivery: A Nanoarchitectonics Perspective
Ferhan, A. R., Park, S.-H., Park, H., Tae, H., Jackman, J. A., & Cho, N. (2022) · Advanced Functional Materials · doi:10.1002/adfm.202203669 · Cited by 103
Tang, C., Jing, W., Han, K. S., Yang, Z., Zhang, S., Liu, M., Zhang, J., Zhao, X., Liu, Y., Shi, C., et al. (2024) · ACS Nano · doi:10.1021/acsnano.3c10109 · Cited by 101
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
Weibull β value for the discernment of drug release mechanism of PLGA particles
Martín-Camacho, U. D. J., Rodríguez-Barajas, N., Sánchez-Burgos, J. A., & Larios, A. P. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.123017 · Cited by 99
Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection
Vaca, G. B., Meyer, M., Cadete, A., Hsiao, C. J., Golding, A. S., Jeon, A. B., Jacquinet, E., Azcue, E., Guan, C. M., Sanchez-Felix, X., et al. (2023) · Science Advances · doi:10.1126/sciadv.adh1655 · Cited by 101
A Combinatorial Library of Lipid Nanoparticles for Cell Type‐Specific mRNA Delivery
Naidu, G. S., Yong, S., Ramishetti, S., Rampado, R., Sharma, P., Ezra, A., Goldsmith, M., Hazan‐Halevy, I., Chatterjee, S., Aitha, A., et al. (2023) · Advanced Science · doi:10.1002/advs.202301929 · Cited by 104
Zhang, C., Ma, Y., Zhang, J., Kuo, J. C., Zhang, Z., Xie, H., Zhu, J., & Liu, T. (2022) · Molecules · doi:10.3390/molecules27061943 · Cited by 95
“5, in which condition the ionizable lipids become positively charged and are able to interact with the endosomal membrane, helping nucleic acids escape from the endosome [110,177].”
BackgroundHan, X., Alameh, M., Gong, N., Xue, L., Ghattas, M., Bojja, G., Xu, J., Zhao, G., Warzecha, C. C., Padilla, M. S., et al. (2024) · Nature Chemistry · doi:10.1038/s41557-024-01557-2 · Cited by 100
“Additionally, ester bond-bearing tails are highly recommended for in vivo applications owing to their degradability 9,11 .”
BackgroundDevelopment 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
“Leukocytes represent a major therapeutic target because of their pivotal role in the immune system and their involvement in various diseases, including cancer, chronic in-fl ammation, and autoimmune disorders [14].”
BackgroundInfluentialXiong, 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
Wang, Y., Li, S., Hu, M., Yang, Y., McCabe, E., Zhang, L., Withrow, A. M., Ting, J. P. ‐., & Liu, R. (2024) · Nature Nanotechnology · doi:10.1038/s41565-024-01624-2 · Cited by 99
mRNA: A Novel Avenue to Antibody Therapy?
Schlake, T., Thran, M., Fiedler, K., Heidenreich, R., Petsch, B., & Fotin‐Mleczek, M. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.03.002 · Cited by 93
“injection of mRNA-LNP lasted for several weeks, suggesting the absence of ADA.(42) However, Pardi et al.”
BackgroundInfluentialFrameworks for transformational breakthroughs in RNA-based medicines
Androsavich, J. R. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-00943-2 · Cited by 100
“Newer lipids incorporating esters to enhance degradation are now preferred, especially for shorter-lived cargos 116,117 .”
Fei, Y., Yu, X., Liu, P., Ren, H., Wei, T., & Cheng, Q. (2024) · Advanced Materials · doi:10.1002/adma.202409812 · Cited by 99
Lim, S., Khoo, R., Juang, Y.-C., Gopal, P., Zhang, H., Yeo, C., Peh, K. M., Teo, J., Ng, S., Henry, B., et al. (2021) · ACS Central Science · doi:10.1021/acscentsci.0c01337 · Cited by 80
Branching Ionizable Lipids Can Enhance the Stability, Fusogenicity, and Functional Delivery of mRNA
Hashiba, K., Sato, Y., Taguchi, M., Sakamoto, S., Otsu, A., Maeda, Y., Shishido, T., Murakawa, M., Arimichi, O., & Harashima, H. (2022) · Small Science · doi:10.1002/smsc.202200071 · Cited by 91
Treatment of Hemophilia A Using Factor VIII Messenger RNA Lipid Nanoparticles
Chen, C.-Y., Tran, D. M., Cavedon, A., Cai, X., Rajendran, R., Lyle, M. J., Martini, P. G. V., & Miao, C. H. (2020) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2020.03.015 · Cited by 89
“The opsonized LNPs bound to apolipoprotein E (ApoE) and low-density lipoprotein (LDL) receptors and facilitated specific uptake of LNPs by hepatocytes.(44,45) In addition, the formulation of F8 LNPs incorporated a “diffusible” polyethylene glycol (PEG) lipid that can shed from the LNP particle to significantly improve…”
BackgroundA New Era for Rare Genetic Diseases: Messenger RNA Therapy
Martini, P. G. V., & Guey, L. T. (2019) · Human Gene Therapy · doi:10.1089/hum.2019.090 · Cited by 88
“In vitro studies evaluating MUT mRNA 16 showed that the mRNA-encoded protein was enzymatically active and had the correct subcellular localization in mitochondria in mut 0 patient fibroblasts.”
Escalona-Rayo, O., Zeng, Y., Knol, R. A., Kock, T. J. F., Aschmann, D., Slütter, B., & Kros, A. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115065 · Cited by 89
John, R., monpara, J., Swaminathan, S., & Kalhapure, R. S. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16010131 · Cited by 99
“Notably, even though MC3 is not fully biodegradable, and its metabolites endure in rats and non-human primates, the doses necessary for clinical use do not exhibit any signs of toxicity [154].”
Long-term efficacy and safety of mRNA therapy in two murine models of methylmalonic acidemia
An, D., Frassetto, A., Jacquinet, E., Eybye, M., Milano, J., DeAntonis, C., Nguyen, V., Laureano, R., Milton, J., Sabnis, S., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.07.003 · Cited by 87
“Moreover, minimal elevations in inflammatory markers including complement and cytokines have been observed in repeat dose toxicology studies conducted in cynomolgus monkeys receiving mRNA encapsulatedwith a similar LNP (1mg/kg) [23].”
BackgroundSelf-citationAdvancements in mRNA Encoded Antibodies for Passive Immunotherapy
Deal, C. E., Carfı́, A., & Plante, O. J. (2021) · Vaccines · doi:10.3390/vaccines9020108 · Cited by 90
“Work on mRNA-encoded protein expression and demonstration of its efficacy in mice and NHPs as well as expression and safety in humans has paved the way for mRNA-encoded antibodies. mRNA delivery with LNPs and the discovery of new and better-tolerated lipids have enabled a substantial increase in antibody expression in…”
BackgroundInfluentialDavies, N. M., Hovdal, D., Edmunds, N. J., Nordberg, P., Dahlén, A., Dabkowska, A. P., Arteta, M. Y., Rădulescu, A., Kjellman, T., Höijer, A., et al. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.03.008 · Cited by 93
“To enable efficient entrapment of the steroid within the LNP, aliphatic ester prodrugs with varying alkyl chain lengths (C5 [rofleponide only], C8 [budesonide only], C14, C16, and C18) were synthesized to increase the lipophilicity/decrease aqueous solubility of the steroids and thereby promote their incorporation wit…”
BackgroundInfluentialThe role of protein corona on nanodrugs for organ-targeting and its prospects of application
Wang, S., Zhang, J., Zhou, H., Lu, Y. C., Jin, X., Luo, L., & Jian, Y. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.06.014 · Cited by 85
Ripoll, M., Bernard, M., Vaure, C., Bazin, E., Commandeur, S., Perkov, V., Lemdani, K., Nicolaï, M., Bonifassi, P., Kichler, A., et al. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121570 · Cited by 89
mRNA lipid nanoparticle phase transition
Trollmann, M. F. W., & Böckmann, R. A. (2022) · Biophysical Journal · doi:10.1016/j.bpj.2022.08.037 · Cited by 86
Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles
Brown, D. W., Wee, P., Bhandari, P., Bukhari, A. B., Grin, L., Vega, H., Hejazi, M., Sosnowski, D. L., Ablack, J., Clancy, E. K., et al. (2024) · Cell · doi:10.1016/j.cell.2024.07.023 · Cited by 84
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
Paloncýová, M., Čechová, P., Šrejber, M., Kührová, P., & Otyepka, M. (2021) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.1c03109 · Cited by 82
Rational design of anti‐inflammatory lipid nanoparticles for mRNA delivery
Zhang, H., Han, X., Alameh, M., Shepherd, S. J., Padilla, M. S., Xue, L., Butowska, K., Weissman, D., & Mitchell, M. J. (2022) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37356 · Cited by 83
A comprehensive comparison of DNA and RNA vaccines
Wang, C., & Yuan, F. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115340 · Cited by 90
Soltanmohammadi, F., Gharehbaba, A. M., Zangi, A. R., Adibkia, K., & Javadzadeh, Y. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117248 · Cited by 87
mRNA in cancer immunotherapy: beyond a source of antigen
Hoecke, L. V., Verbeke, R., Dewitte, H., Lentacker, I., Vermaelen, K. Y., Breckpot, K., & Lint, S. V. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01329-3 · Cited by 85
Lipid Nanoparticle Delivery Systems to Enable mRNA-Based Therapeutics
Semple, S. C., Leone, R. D., Barbosa, C., Tam, Y. K., & Lin, P. J. C. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14020398 · Cited by 80
Suzuki, Y., Miyazaki, T., Muto, H., Kubara, K., Mukai, Y., Watari, R., Sato, S., Kondo, K., Tsukumo, S., Yasutomo, K., et al. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.09.017 · Cited by 83
Nanoparticles as Adjuvants and Nanodelivery Systems for mRNA-Based Vaccines
Alfagih, I. M., Aldosari, B. N., AlQuadeib, B. T., Almurshedi, A. S., & Alfagih, M. M. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics13010045 · Cited by 80
“However, only a small percentage (up to 15%) of the total mRNA loaded into the internalized lipid nanoparticles is reported to actually reach the cytoplasm through this pathway depending on the fusogenicity of the ionizable lipid used [84,85].”
BackgroundHan, X., Xu, J., Xu, Y., Alameh, M., Xue, L., Gong, N., El-Mayta, R. D., Palanki, R., Warzecha, C. C., Zhao, G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45537-z · Cited by 85
“1a and S2), since previous studies have suggested that small-molecule metabolites tend to undergo rapid elimination 16,20 .”
BackgroundMethodInfluentialSelf-Amplifying RNA Approach for Protein Replacement Therapy
Papukashvili, D., Rcheulishvili, N., Liu, C., Ji, Y., He, Y., & Wang, P. G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112884 · Cited by 76
“These LNPs contain about 100 mRNA molecules per LNP [84] and are 80–100 nm in diameter [85,86].”
BackgroundLi, Z., Zhang, X., Ho, W., Li, F., Gao, M., Bai, X., & Xu, X. (2022) · ACS Nano · doi:10.1021/acsnano.2c07822 · Cited by 79
Spray dried lipid nanoparticle formulations enable intratracheal delivery of mRNA
Friis, K. P., Gracin, S., Oag, S., Leijon, A., Sand, E., Lindberg, B., Lázaro‐Ibáñez, E., Lindqvist, J., Whitehead, K. A., & Bak, A. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.09.031 · Cited by 79
Walther, J., Porenta, D., Wilbie, D., Seinen, C. W., Benne, N., Yang, Q., de Jong, O. G., Lei, Z., & Mastrobattista, E. (2024) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2024.114207 · Cited by 80
Wei, G., Cao, J., Huang, P., An, P., Skelton-Badlani, D., Vaid, K. A., Zhao, S., Wang, D. Q. ‐., Zhuo, J., Yin, L., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.12.010 · Cited by 74
Sarode, A., Fan, Y., Byrnes, A. E., Hammel, M., Hura, G. L., Fu, Y., Kou, P., Hu, C., Hinz, F. I., Roberts, J., et al. (2022) · Nanoscale Advances · doi:10.1039/d1na00712b · Cited by 78
“25,56,57 To systematically understand the e ff ect of PEG-lipid properties on LNP cargo delivery, several PEG-lipid analogs were incorporated into the ASO-LNPs (Table 1).”
mRNA vaccines: Past, present, future
Karam, M., & Daoud, G. (2022) · Asian Journal of Pharmaceutical Sciences · doi:10.1016/j.ajps.2022.05.003 · Cited by 76
“5) Phase I/II clinical trial (NCT03480152) - Induction of CD4 + and CD8 + mutation-specific T cell responses against predicted neoepitopes [47 ,48]”
BackgroundThe mRNA Vaccine Revolution: COVID-19 Has Launched the Future of Vaccinology
Ye, Z., Harmon, J., Ni, W., Li, Y., Wich, D., & Xu, Q. (2023) · ACS Nano · doi:10.1021/acsnano.2c12584 · Cited by 72
tRNA therapeutics for genetic diseases
Coller, J., & Ignatova, Z. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00829-9 · Cited by 72
“137) which demonstrated no apparent toxicity following systemic administration in animal models of acute intermittent porphyria 138 , or following local intratumoral administration of IL-23, IL-36γ and OX40L mRNAs 139 .”
Han, X., Alameh, M., Xu, Y., Palanki, R., El-Mayta, R. D., Dwivedi, G., Swingle, K. L., Xu, J., Gong, N., Xue, L., et al. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01267-7 · Cited by 78
“Similarly, Moderna developed lipid 5 to lipid H (SM-102) and then to their newest lead candidate lipid 29 over the course of several years 26,37,38 .”
InfluentialRecent advances in polymeric materials for the delivery of RNA therapeutics
Ulkoski, D., Bak, A., Wilson, J. T., & Krishnamurthy, V. R. (2019) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2019.1663822 · Cited by 74
Protein 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
An optimized messenger RNA vaccine candidate protects non-human primates from Zika virus infection
Bollman, B. A., Nunna, N., Bahl, K., Hsiao, C. J., Bennett, H., Butler, S., Foreman, B. M., Burgomaster, K. E., Aleshnick, M., Kong, W., et al. (2023) · npj Vaccines · doi:10.1038/s41541-023-00656-4 · Cited by 72
“The formulations were dialyzed against phosphate-buffered saline (pH 7.4) for 18 hours, concentrated, and passed through a 0.22-µm fi lter before storage at 4 °C. Final particle size and encapsulation were <100 nm and >80%, respectively, with endotoxin below 10 EU/mL 50 .”
InfluentialIn vivo fate and intracellular trafficking of vaccine delivery systems
Lee, J., Kim, D., Byun, J., Wu, Y., Park, J.-W., & Oh, Y. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114325 · Cited by 72
“This enhanced biodegradability was shown to remarkably accelerate the degradation and excretion of lipid nanoparticles [79-81].”
He, Z., Le, Z., Shi, Y., Liu, L., Liu, Z., & Chen, Y. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202310401 · Cited by 72
Lipid shape and packing are key for optimal design of pH-sensitive mRNA lipid nanoparticles
Tesei, G., Hsiao, Y., Dabkowska, A. P., Grönberg, G., Arteta, M. Y., Ulkoski, D., Bray, D. J., Trulsson, M., Ulander, J., Lund, M., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2311700120 · Cited by 70
“Experimental evidence indicates a significant uptake of LNPs through ApoE - LDLr receptor - mediated endocytosis (3, 4), whereas the main bottleneck for LNP delivery is attributed to the endosomal escape (5, 6).”
BackgroundmRNA Therapy Improves Metabolic and Behavioral Abnormalities in a Murine Model of Citrin Deficiency
Cao, J., An, D., Galduroz, M., Zhuo, J., Liang, S., Eybye, M., Frassetto, A., Kuroda, E., Funahashi, A., Santana, J., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.04.017 · Cited by 70
“We have coupled these novel lipids with advances in mRNA chemistry and design to enable both the safe and effective delivery of mRNA in vivo.(19,22) To assess whether this system delivers hCitrin-mRNAWT in vivo to mouse livers, we injected normal C57BL/6 mice intravenously (i.”
MethodSelf-citationDelivery of therapeutic oligonucleotides in nanoscale
Wu, L., Zhou, W., Lin, L., Chen, A., Feng, J. C., Qu, X., Zhang, H., & Yue, J. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.05.038 · Cited by 72
Regulatory guidelines and preclinical tools to study the biodistribution of RNA therapeutics
Vervaeke, P., Borgos, S. E., Sanders, N. N., & Combes, F. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114236 · Cited by 79
“Additionally, the use of biodegradable lipids can aid in reducing accumulation of these drug components [44,45].”
Zhang, H., & Barz, M. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.02.055 · Cited by 80
Development of a high-throughput platform for screening lipid nanoparticles for mRNA delivery
Cui, L., Pereira, S. G. T., Sonzini, S., van Pelt, S., Romanelli, S. M., Liang, L., Ulkoski, D., Krishnamurthy, V. R., Brannigan, E., Brankin, C., et al. (2022) · Nanoscale · doi:10.1039/d1nr06858j · Cited by 72
Cardoso, R. V., Pereira, P. R., Freitas, C. S., & Paschoalin, V. M. F. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14122808 · Cited by 69
Ionizable Lipid Nanoparticles for mRNA Delivery
Tang, X., Zhang, Y., & Han, X. (2023) · Advanced NanoBiomed Research · doi:10.1002/anbr.202300006 · Cited by 76
A lipid nanoparticle platform for mRNA delivery through repurposing of cationic amphiphilic drugs
Bogaert, B., Sauvage, F., Guagliardo, R., Muntean, C., Nguyen, V. P., Pottie, E., Wels, M., Minnaert, A., Rycke, R. M. D., Yang, Q., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.08.009 · Cited by 69
Lipid nanoparticle-mediated messenger RNA delivery for ex vivo engineering of natural killer cells
Douka, S., Brandenburg, L. E., Casadidio, C., Walther, J., Garcia, B. B. M., Spanholtz, J., Raimo, M., Hennink, W. E., Mastrobattista, E., & Caiazzo, M. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.08.014 · Cited by 70
Metadata
- Authors
- Sabnis, S., Kumarasinghe, E. S., Salerno, T., Mihai, C., Ketova, T., Senn, J. J., Lynn, A., Bulychev, A., McFadyen, I., Chan, J., Almarsson, Ö., Stanton, M. G., & Benenato, K. E.
- Affiliations
- Moderna Therapeutics (United States) (US)
- Corresponding author
- Benenato, Kerry E.
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 26
- Issue
- 6
- Pages
- 1509-1519
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC5986714
- OpenAlex
- W2791854174
- Cited by
- 820
- References
- 20
- Citations by year
- 2026: 107 · 2025: 139 · 2024: 156 · 2023: 139 · 2022: 116 · 2021: 73 · 2020: 51 · 2019: 31 · 2018: 7
- FWCI
- 14.41
- 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)
- 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 › Advancements in Transdermal Drug Delivery
- Keywords
- mRNA delivery, lipid nanoparticles, endosomal escape, structure-activity relationship, pharmacokinetics, toxicology, non-human primates
- MeSH terms
- Animals, Lipids, Primates, RNA, Messenger, Rats, Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
