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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.
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“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
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Items 301–400 of 820
Bartesaghi, S., Wallenius, K., Hovdal, D., Liljeblad, M., Wallin, S., Dekker, N., Barlind, L., Davies, N. M., Seeliger, F., Winzell, M. S., et al. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.04.010 · Cited by 40
“LNPs were formulated using a biodegradable, ionizable lipid (lipid 5, as previously described in Sabnis et al.(21)), cholesterol, distearoylphosphatidylcholine, and dimyryristoylphosphatidylcholine polyethyleneglycol 2000 at a percent molar composition of 50:38.”
BackgroundMethodInfluentialHuang, X., Chuang, L. I. U., Sharma, S. N., You, X., Chen, S., Li, Y., Liu, H.-J., Liu, B., Saiding, Q., Chen, W., et al. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adu1493 · Cited by 39
Lipid Nanoparticles for mRNA Delivery to Enhance Cancer Immunotherapy
Wang, H., Wang, Z.-G., & Liu, S. (2022) · Molecules · doi:10.3390/molecules27175607 · Cited by 41
Zhao, Y., Tian, Y. E., Ye, W., Wang, X., Huai, Y., Huang, Q., Chu, X., Deng, X., & Qian, A. (2022) · Biomaterials Science · doi:10.1039/d2bm01454h · Cited by 38
Minimizing the ratio of ionizable lipid in lipid nanoparticles for in vivo base editing
Chen, Q., Wang, X., Zhang, Y., Tian, M., Duan, J., Zhang, Y., & Yin, H. (2024) · National Science Review · doi:10.1093/nsr/nwae135 · Cited by 41
“SM-102 efficiently targets the liver after intravenous injection of its formulated LNP [29 ,32 ,37 –39 ].”
BackgroundResultInfluentialWu, K., Xu, F., Dai, Y., Jin, S., Zheng, A., Zhang, N., & Xu, Y. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.11.007 · Cited by 37
Alshehry, Y., Liu, X., Zhang, Y., & Zhu, G. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.113617 · Cited by 39
Efficient mRNA delivery to resting T cells to reverse HIV latency
Cevaal, P. M., Kan, S., Fisher, B. M., Moso, M. A., Tan, A., Liu, H., Ali, A., Tanaka, K., Shepherd, R. A., Kim, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60001-2 · Cited by 38
“First, the ionisable lipid DLin-MC3-DMA (MC3) was replaced with SM-102, an ionisable lipid previously shown to lead to greater cytosolic mRNA delivery through enhanced endosomal escape 30 .”
Rational design of lipid nanoparticles for enabling gene therapies
Brimacombe, C. A., Kulkarni, J. A., Cheng, M. H. Y., An, K., Witzigmann, D., & Cullis, P. R. (2025) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2025.101518 · Cited by 45
“131 Active squaramide ionizable amino lipids have been identified that exhibit hydrogen bonding and pi stacking with mRNA.”
InfluentialZhang, H., Bussmann, J., Huhnke, F. H., Devoldere, J., Minnaert, A., Jiskoot, W., Serwane, F., Spatz, J. P., Röding, M., Smedt, S. C. D., et al. (2021) · Advanced Science · doi:10.1002/advs.202102072 · Cited by 37
Nanoparticles Loaded with Platinum Drugs for Colorectal Cancer Therapy
Buyana, B., Naki, T., Alven, S., & Aderibigbe, B. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911261 · Cited by 39
“LNPs are multicomponent systems containing poly(ethylene glycol) (PEG)-lipid, cholesterol, phospholipid, and amino lipid [96,97].”
BackgroundNovel Ionizable Lipid Nanoparticles for SARS‐CoV‐2 Omicron mRNA Delivery
Long, J., Yu, C., Zhang, H., Cao, Y., Sang, Y., Lü, H., Zhang, Z., Wang, X., Wang, H., Song, G., et al. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202202590 · Cited by 36
Ci, L., Hard, M., Zhang, H., Gandham, S. K., Hua, S. S., Wickwire, J., Wehrman, T., Slauter, R., Auerbach, A. D., Kenney, M., et al. (2023) · Drug Metabolism and Disposition · doi:10.1124/dmd.122.000980 · Cited by 39
“Lipid 5 was synthesized as previously described (Sabnis et al., 2018) and labeled with 14C at the proximal carbon of the ethanolamine aliphatic chain linked to the tertiary nitrogen (Eurofins; Columbia, MO; Fig.”
MethodInfluentialSelf-citationYan, J., Zhang, H., Li, G., Su, J., Wei, Y., & Xu, C. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.10.012 · Cited by 40
“In contrast, a higher percentage of mRNAs than siRNAs have been reported to be released from endosomes, with some studies reporting 15%, which depended on ionizable lipid fusoge-nicity 61,136 .”
BackgroundResultInfluentialSilicon Ether Ionizable Lipids Enable Potent mRNA Lipid Nanoparticles with Rapid Tissue Clearance
Holland, R., Lam, K., Jeng, S. C. Y., McClintock, K., Palmer, L., Schreiner, P., Wood, M., Zhao, W., & Heyes, J. A. (2024) · ACS Nano · doi:10.1021/acsnano.3c09028 · Cited by 38
Bian, X., Yang, L., Jiang, D., Grippin, A., Ma, Y., Wu, S., Wu, L., Wang, X., Tang, Z., Tang, K., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48461-4 · Cited by 41
“The potential cytotoxicity of ionizable lipids has raised broad concerns 30 , and discontinuous measurements and end-point data collection do not re fl ect time-varying, dynamic changes.”
Yoon, I., Xue, L., Chen, Q., Liu, J., Xu, J., Siddiqui, Z., Kim, D., Chen, B., Shi, Q., Han, E. L., et al. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202415389 · Cited by 39
Property-Driven Design and Development of Lipids for Efficient Delivery of siRNA
Rajappan, K., Tanis, S. P., Mukthavaram, R., Roberts, S., Nguyen, M., Tachikawa, K., Sagi, A., Sablad, M., Limphong, P., Leu, A. I., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01407 · Cited by 38
Synthetic mRNA – emerging new class of drug for tissue regeneration
Balmayor, E. R. (2021) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2021.10.015 · Cited by 36
Development of an extended half-life GM-CSF fusion protein for Parkinson's disease
Yeapuri, P., Olson, K. E., Lu, Y., Abdelmoaty, M. M., Namminga, K. L., Marković, M., Machhi, J., Mosley, R. L., & Gendelman, H. E. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.06.024 · Cited by 36
Medjmedj, A., Loth, A. N., Clémençon, R., Hamáček, J., Pichon, C., & Perche, F. (2022) · Nanomaterials · doi:10.3390/nano12142446 · Cited by 39
siRNA delivery to lymphatic endothelial cells via ApoE-mediated uptake by lipid nanoparticles
Sakurai, Y., Yoshikawa, K., Arai, K., Kazaoka, A., Aoki, S., Ito, K., Nakai, Y., Tange, K., Furihata, T., Tanaka, H., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.11.036 · Cited by 36
Kim, M., Jeong, M., Lee, G., Lee, Y., Park, J., Jung, H., Im, S., Yang, J., Kim, K., & Lee, H. (2023) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10556 · Cited by 35
“8 On the other hand, MCP-1 is an important chemokine for the initiation of inflammation.”
BackgroundMethodInfluentialChambers, C., Soo, G. L., Engel, A. L., Glass, I. A., Frassetto, A., Martini, P. G. V., & Cherry, T. J. (2024) · Translational Vision Science & Technology · doi:10.1167/tvst.13.7.7 · Cited by 36
“17,18 We aimed to characterize the ability of these engineered mRNA LNPs to transfect retinal cells in both in vivo and ex vivo systems.”
BackgroundHourdel, L., Lebaz, N., Peral, F., Ripoll, M., Briançon, S., Bensaid, F., Luthra, S., & Cogné, C. (2025) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2025.125297 · Cited by 37
Non-viral nucleic acid delivery approach: A boon for state-of-the-art gene delivery
Sahu, K. K., Pradhan, M., Singh, D., Singh, M. R., & Yadav, D. K. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.104152 · Cited by 36
Optimization of ionizable lipids for aerosolizable mRNA lipid nanoparticles
Lewis, M. M., Soto, M. R., Maier, E. Y., Wulfe, S., Bakheet, S., Obregon, H., & Ghosh, D. (2023) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10580 · Cited by 36
“62 Therefore, we retained these properties and instead focused on small changes in other carbon structures.”
BackgroundHosseini-Kharat, M., Bremmell, K. E., Grubor‐Bauk, B., & Prestidge, C. A. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.12.002 · Cited by 37
Panova, E. A., Kleymenov, D. A., Shcheblyakov, D. V., Bykonia, E. N., Mazunina, E. P., Dzharullaeva, A. S., Zolotar, A. N., Derkaev, A. A., Esmagambetov, I. B., Sorokin, I. I., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1098302 · Cited by 35
“has previously been shown to be very effective for this purpose, providing robust protein synthesis [31,33].”
BackgroundDevelopment of nucleic acid medicines based on chemical technology
Kawamoto, Y., Wu, Y., Takahashi, Y., & Takakura, Y. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114872 · Cited by 34
Yazdi, M., Pöhmerer, J., Kafshgari, M. H., Seidl, J., Grau, M., Höhn, M., Vetter, V., Hoch, C. C., Wollenberg, B., Multhoff, G., et al. (2024) · Small · doi:10.1002/smll.202400643 · Cited by 36
Targeting and tracking mRNA lipid nanoparticles at the particle, transcript and protein level
Kang, D. D., Marks, A. R., Morlà‐Folch, J., Dong, Y., Brown, B. D., & Teunissen, A. J. P. (2025) · Nature Biomedical Engineering · doi:10.1038/s41551-025-01511-8 · Cited by 45
“An ethanolamine amino head group was reported to confer high mRNA-encapsulation efficiency and other desirable LNP properties 93 , which encouraged the testing of ionizable lipids comprising this head group and various lipid tails.”
High-Throughput Automation of Endosomolytic Polymers for mRNA Delivery
Ulkoski, D., Munson, M. J., Jacobson, M. E., Palmer, C. R., Carson, C. S., Sabirsh, A., Wilson, J. T., & Krishnamurthy, V. R. (2021) · ACS Applied Bio Materials · doi:10.1021/acsabm.0c01463 · Cited by 34
Spleen-targeted nanosystems for immunomodulation
Wang, F., Lou, J., Gao, X., Zhang, L., Sun, F., Wang, Z., Ji, T., & Qin, Z. (2023) · Nano Today · doi:10.1016/j.nantod.2023.101943 · Cited by 36
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Jiang, Z., Xu, Y., Du, G., & Sun, X. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.04.039 · Cited by 35
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Wu, S., Su, K., Yan, X., Shi, L., Lin, L., Ren, E., Zhou, J., Zhang, C., Song, Y., & Liu, S. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.10.028 · Cited by 35
Abostait, A., Abdelkarim, M., Bao, Z., Miyake, Y., Tse, W. H., Ciano‐Oliveira, C. D., Buerki‐Thurnherr, T., Allen, C. J., Keijzer, R., & Labouta, H. I. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.10.047 · Cited by 34
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“…of composition and size on the internal architecture of full - sized LNPs is needed, with a special focus on the LNP structure in the maturing endosome, since this is where the process of endosomal escape takes place, which is known to be a crucial bottleneck in functional RNA delivery ( 22 , 23 ).”
Lam, P. Y., Omer, N., Wong, J., Tu, C., Alim, L., Rossi, G. R., Victorova, M., Tompkins, H., Lin, C., Mehdi, A. M., et al. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70140 · Cited by 35
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Paloncýová, M., Valério, M., dos Santos, R. N., Kührová, P., Šrejber, M., Čechová, P., Dobchev, D. A., Balsubramani, A., Banáš, P., Agarwal, V., et al. (2025) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.4c00744 · Cited by 35
Lian, Z., Zheng, L., Liu, S., Zhang, J., Zhou, J. J., Wu, J., Ouyang, S., Li, J., & Yang, H. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c05367 · Cited by 35
Therapeutic strategies for acute intermittent porphyria
Zhao, L., Wang, X., Zhang, X., Liu, X., Ma, N., Zhang, Y., & Zhang, S. (2020) · Intractable & Rare Diseases Research · doi:10.5582/irdr.2020.03089 · Cited by 36
“On day 10 postinjection, this protein is still detectable, indicating that it can remain in the liver for a long time (116).”
BackgroundNano‐Oncologicals: A Tortoise Trail Reaching New Avenues
Dacoba, T. G., Anthiya, S., Berrecoso, G., Fernández‐Mariño, I., Fernández‐Varela, C., Crecente‐Campo, J., Teijeiro‐Osorio, D., Torres, F., & Alonso, M. J. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202009860 · Cited by 34
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Abbasi, S., & Uchida, S. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13050644 · Cited by 33
Sohi, A. N., Kiani, J., Arefian, E., Khosrojerdi, A., Fekrirad, Z., Ghaemi, S., Zim, M. K., Jalili, A., Bostanshirin, N., & Soleimani, M. (2021) · Vaccines · doi:10.3390/vaccines9091007 · Cited by 32
Gallud, A., Munson, M. J., Liu, K., Idström, A., Barriga, H. M. G., Tabaei, S. R., Aliakbarinodehi, N., Ojansivu, M., Lubart, Q., Doutch, J., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.20.457104 · Cited by 35
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“However, these technologies present challenges; cationic liposomes, for instance, may induce cytotoxicity and immune activation [78–84].”
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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 · doi:10.1002/ange.202004994 · Cited by 32
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Effects of oncolytic viruses and viral vectors on immunity in glioblastoma
Liu, P., Wang, Y., Wang, Y., Kong, Z., Chen, W., Li, J., Chen, W., Wang, Y., Ma, W., & Wang, Y. (2020) · Gene Therapy · doi:10.1038/s41434-020-00207-9 · Cited by 32
Wibel, R., Knoll, P., Le‐Vinh, B., Kali, G., & Bernkop‐Schnürch, A. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.03.013 · Cited by 32
Chung, C. W., Kudchodkar, S. B., Chung, C. N., Park, Y. K., Xu, Z., Pardi, N., Abdel‐Mohsen, M., & Muthumani, K. (2023) · Antibodies · doi:10.3390/antib12030046 · Cited by 36
“anti-Influenza A 1-methylpseudouridine cynomolgus monkeys LNP, IV [98]”
BackgroundVlasova, K. Y., Kerr, A., Pennock, N. D., Jozić, A., Sahel, D. K., Gautam, M., Murthy, N. T. V., Roberts, A., Ali, M. W., MacDonald, K. D., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59136-z · Cited by 35
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Zhang, M., Hussain, A., Yang, H., Zhang, J., Liang, X., & Huang, Y. (2022) · Nano Research · doi:10.1007/s12274-022-4627-5 · Cited by 35
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Byun, J., Wu, Y., Park, J.-W., Kim, J. S., Li, Q., Choi, J., Shin, N., Lan, M., Cai, Y., Lee, J., et al. (2023) · The AAPS Journal · doi:10.1208/s12248-023-00860-z · Cited by 32
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Jha, S. K., Imran, M., Jha, L. A., Hasan, N., Panthi, V. K., Paudel, K. R., Almalki, W. H., Mohammed, Y., & Kesharwani, P. (2023) · Environmental Research · doi:10.1016/j.envres.2023.116823 · Cited by 32
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“128,129 Sabnis et al. showed that while LNPs containing MC3 amino lipid demonstrated better in vitro uptake of the LNPs, the resultant amount of cytosolic mRNA detected per cell was much lower (EE: 2.5%), compared with Lipid 5-based LNPs, which had a lower LNP uptake but with a much higher…”
InfluentialSoni, S., Kori, S. K., Nema, P., Iyer, A. K., Soni, V., & Kashaw, S. K. (2024) · Current Medicinal Chemistry · doi:10.2174/0109298673278936240107121907 · Cited by 31
Robust genome and cell engineering via in vitro and in situ circularized RNAs
Tong, M., Palmer, N. D., Dailamy, A., Kumar, A., Khaliq, H., Han, S., Finburgh, E. N., Wing, M. K., Hong, C., Xiang, Y., et al. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01245-z · Cited by 32
Nanomedicines with Versatile GSH-Responsive Linkers for Cancer Theranostics
Ding, H., Zhou, C., & Li, T. (2024) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.4c00897 · Cited by 29
Chen, B., Chen, Y., Li, J., Wang, C., Song, W., Wen, Y., Lin, J., Wu, Y., & Ying, T. (2022) · mBio · doi:10.1128/mbio.01612-22 · Cited by 33
“modification (8, 9), and delivery technology (10, 11) have been developed for decades,”
BackgroundMethodUse, exposure and omics characterisation of potential hazard in nanomaterials
Ling, N., Zhang, N., Yong, W. T. L., Misbah, S., Hashim, F., Soon, C. F., Lim, G. P., Peng, W., & Sonne, C. (2023) · Materials Today Advances · doi:10.1016/j.mtadv.2023.100341 · Cited by 31
Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders
Arjunan, P., Kathirvelu, D., Mahalingam, G., Goel, A., Zacharaiah, U. G., Srivastava, A., & Marepally, S. K. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.04.015 · Cited by 33
“A novel series of amino lipids could efficiently deliver luciferase mRNA in rodents and nonhuman primates without adverse events 132 .”
BackgroundBeigi, A., Naghib, S. M., Matini, A., Tajabadi, M., & Mozafari, M. R. (2024) · Current Gene Therapy · doi:10.2174/0115665232292768240503050508 · Cited by 30
Zhao, Y., Wang, Z. M., Song, D., Chen, M., & Xu, Q. (2024) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2024.102499 · Cited by 30
Elwakil, M. M. A., Suzuki, R., Khalifa, A. M., Elshami, R. M., Isono, T., Elewa, Y. H. A., Sato, Y., Nakamura, T., Satoh, T., & Harashima, H. (2023) · Advanced Functional Materials · doi:10.1002/adfm.202303795 · Cited by 30
Taylor Dispersion Analysis to support lipid-nanoparticle formulations for mRNA vaccines
Malburet, C., Leclercq, L., Cotte, J., Thiebaud, J., Bazin, E., Garinot, M., & Cottet, H. (2022) · Gene Therapy · doi:10.1038/s41434-022-00370-1 · Cited by 29
“Yet, some points still need to be optimized such as the stability of the formulations [15, 16], the endosomal escape efficiency [17, 18], the reduction of reactogenicity and adverse events after injection [19], and the precise targeting of certain organs [20–22].”
BackgroundMartini 3 Building Blocks for Lipid Nanoparticle Design
Kjølbye, L. R., Valério, M., Paloncýová, M., Borges-Araújo, L., Pestana-Nobles, R., Grünewald, F., Bruininks, B. M. H., Araya‐Osorio, R., Šrejber, M., Mera‐Adasme, R., et al. (2025) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.5c01207 · Cited by 28
Design principles of lipid nanoparticles for RNA delivery
Arral, M. L., & Whitehead, K. A. (2026) · Nature Reviews Bioengineering · doi:10.1038/s44222-026-00401-1 · Cited by 41
“Although helper lipids were absent from early iterations of lipidoid nanoparticles for siRNA delivery 45,53 , they have long been standard components in nanoparticles made from two-tailed ionizable lipids 35,73 .”
InfluentialLipid Nanoparticles for Broad‐Spectrum Nucleic Acid Delivery
Hejdankova, Z., Vaněk, V., Sedlák, F., Procházka, J., Diederichs, A., Kereı̈che, S., Novotná, B., Buděšı́nský, M., Birkuš, G., Šašková, K. G., et al. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202101391 · Cited by 27
Recent Advances in RNA Therapy and Its Carriers to Treat the Single-Gene Neurological Disorders
Lee, M., Lee, I., & Wang, K. (2022) · Biomedicines · doi:10.3390/biomedicines10010158 · Cited by 27
“With endosomal escape, mRNA cargo can be released into the cytoplasm [68].”
BackgroundKhoja, S., Liu, X.-B., Truong, B., Nitzahn, M., Lambert, J., Eliav, A., Nasser, E., Randolph, E., Burke, K. E., White, R. A., et al. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.04.012 · Cited by 26
“, A) with an uptake mechanism that works by an apolipoprotein E (ApoE)-mediated low-density lipoprotein (LDL) receptor-dependent mechanism that has efficient endosomal escape.(23) The interaction of LNPs with serum apolipoproteins, including ApoE, enhances uptake into primary hepatocytes.”
BackgroundLi, M., Wang, Z., Xie, C., & Xia, X. (2022) · International review of cytology · doi:10.1016/bs.ircmb.2022.04.011 · Cited by 30
“advantages, such as protecting mRNA from enzymatic degradation and high delivery efficiency into cell cytosol (Midoux and Pichon, 2015; Richner et al., 2017a; Sabnis et al., 2018).”
BackgroundBepperling, A., & Richter, G. M. (2023) · European Biophysics Journal · doi:10.1007/s00249-023-01663-y · Cited by 33
“Quantifying the number of mRNAs per LNP with single particle imaging microscopy, Sabnis and co-workers (Sabnis et al. 2018) have found a weighted average of 4.”
MethodBiological recognition and cellular trafficking of targeted RNA-lipid nanoparticles
Escalona-Rayo, O., Papadopoulou, P., Slütter, B., & Kros, A. (2023) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2023.103041 · Cited by 28
mRNA cancer vaccines from bench to bedside: a new era in cancer immunotherapy
Shariati, A., Khani, P., Nasri, F., Afkhami, H., Khezrpour, A., Kamrani, S., Shariati, F. S., Alavimanesh, S., & Modarressi, M. H. (2024) · Biomarker Research · doi:10.1186/s40364-024-00692-9 · Cited by 27
Su, L.-J., Wang, N.-N., Luo, R.-S., Ji, Z.-H., Gu, H., Yang, C., Xu, M.-X., Zhang, J., Chen, Q., Yu, M., et al. (2026) · Nature Biomedical Engineering · doi:10.1038/s41551-026-01640-8 · Cited by 33
Application of mRNA Technology in Cancer Therapeutics
Eralp, Y. (2022) · Vaccines · doi:10.3390/vaccines10081262 · Cited by 27
“The structure of the amino lipid component plays a key role in delivery efficacy, tolerance, and tissue clearance [50].”
BackgroundmRNA-delivery of IDO1 suppresses T cell-mediated autoimmunity
Kenney, L. L., Chiu, R. S.-Y., Dutra, M. N., Wactor, A., Honan, C., Shelerud, L. M., Corrigan, J. J., Yu, K. J., Ferrari, J. D., Jeffrey, K. L., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101717 · Cited by 28
Intelligent Design of Lipid Nanoparticles for Enhanced Gene Therapeutics
Yuan, Y., Li, Y., Li, G., Lei, L., Huang, X., Li, M., & Yao, Y. (2025) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.4c00925 · Cited by 28
The design, manufacture and LNP formulation of mRNA for research use
Leighton, L. J., Chaudhary, N., Tompkins, H. E., Kulkarni, A., Carrodus, N. L., Budzinska, M. A., Das, S. L., Cheetham, S. W., & Mercer, T. R. (2025) · Nature Protocols · doi:10.1038/s41596-025-01174-4 · Cited by 24
Pei, Y., Bao, Y., Sacchetti, C., Brady, J., Gillard, K., Yu, H., Roberts, S., Rajappan, K., Tanis, S. P., Pérez‐García, C. G., et al. (2022) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2022.105178 · Cited by 26
CRISPR/Cas9 in the era of nanomedicine and synthetic biology
Schmidt, T. J. N., Berarducci, B., Konstantinidou, S., & Raffa, V. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.103375 · Cited by 26
Cirella, A., Bolaños, E., Trani, C. A. D., de Andrea, C. E., Sánchez‐Gregorio, S., Etxeberría, I., González-Gomariz, J., Olivera, I., Brocco, D., Glez‐Vaz, J., et al. (2022) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-22-0373 · Cited by 25
Goldman, R., Murthy, N. T. V., Trent, N., Balakrishnan, A., Chivukula, S. V., Danz, H., Tibbitts, T. J., Dias, A., Vargas, J., Cooper, D. L., et al. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122243 · Cited by 26
An mRNA-based platform for the delivery of pathogen-specific IgA into mucosal secretions
Deal, C. E., Richards, A. F., Yeung, T., Maron, M. J., Wang, Z., Lai, Y., Fritz, B. R., Himansu, S., Narayanan, E., Liu, D., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101253 · Cited by 25
“20,29,35 The higher level of sialylation observed for IgA2 mRNA is reminiscent of IgA2 isolated from human serum, and this could contribute to increased serum half-life via protection from receptor-mediated clearance.”
BackgroundSurface modification of lipid nanoparticles for gene therapy
Tafech, B., Mohabatpour, F., & Hedtrich, S. (2023) · The Journal of Gene Medicine · doi:10.1002/jgm.3642 · Cited by 25
Nonclinical safety evaluation of a novel ionizable lipid for mRNA delivery
Broudic, K., Amberg, A., Schaefer, M. K., Spirkl, H.-P., Bernard, M., & Désert, P. (2022) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2022.116143 · Cited by 25
A self-amplifying RNA vaccine prevents enterovirus D68 infection and disease in preclinical models
Warner, N. L., Archer, J. F., Park, S., Singh, G., McFadden, K. M., Kimura, T., Nicholes, K., Simpson, A., Kaelber, J. T., Hawman, D. W., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adi1625 · Cited by 26
“The microfluidized LION was terminally filtered with a 200-nm–pore size polyethersulfone filter and stored at 2° to 8°C. RNA was encapsulated into LNPs using methods described previously ( 72 ).”
MethodSchultz, D. P., Münter, R., Cantín, A. M., Kempen, P. J., Jahnke, N., Andresen, T. L., Simonsen, J. B., & Urquhart, A. J. (2024) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2024.114571 · Cited by 23
Distinct Inflammatory Programs Underlie the Intramuscular Lipid Nanoparticle Response
Dowell, W. R., Dearborn, J. S., Languon, S., Miller, Z. D., Kirch, T., Paige, S., Garvin, O., Kjendal, L., Harby, E., Zuchowski, A. B., et al. (2024) · The Journal of Immunology · doi:10.1021/acsnano.4c08490 · Cited by 23
Harnessing mRNA-lipid nanoparticles as innovative therapies for autoimmune diseases
Razavi, R., Kegel, M., Muscat-Rivera, J., Weissman, D., & Melamed, J. R. (2025) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2025.101566 · Cited by 28
Givosiran for the treatment of acute hepatic porphyria
Ricci, A., & Ventura, P. (2022) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2022.2075848 · Cited by 24
Ji, A., Xu, M., Pan, Y., Diao, L., Ma, L., Li, Q., Cheng, J., & Liu, M. (2022) · Pharmaceutical Research · doi:10.1007/s11095-022-03445-1 · Cited by 24
“Sa far, lipid nanoparticles (LNPs) is the most promising and developed technology for mRNA delivery [16, 18, 19].”
Background
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
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