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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
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–300 of 820
Dirisala, A., Uchida, S., Li, J., Guyse, J. F. R. V., Hayashi, K., Vummaleti, S. V. C., Kaur, S., Mochida, Y., Fukushima, S., & Kataoka, K. (2022) · Macromolecular Rapid Communications · doi:10.1002/marc.202100754 · Cited by 67
mRNA: A promising platform for cancer immunotherapy
Kong, B., Kim, Y., Kim, E. H., Suk, J. S., & Yang, Y. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114993 · Cited by 74
Investigations into mRNA Lipid Nanoparticles Shelf-Life Stability under Nonfrozen Conditions
Reinhart, A.-G., Osterwald, A., Ringler, P., Leiser, Y., Lauer, M. E., Martin, R. E., Ullmer, C., Schumacher, F. F., Korn, C., & Keller, M. (2023) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.3c00956 · Cited by 67
Binici, B., Rattray, Z., Zinger, A., & Perrie, Y. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.11.010 · Cited by 73
Padilla, M. S., Mrksich, K., Wang, Y., Haley, R. M., Li, J. J., Han, E. L., El-Mayta, R. D., Kim, E. H., Dias, S., Gong, N., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55137-6 · Cited by 74
“Moreover, ILs expedite endosomal escape, or the process of mRNAs breaking through the endosome and entering the cytosol to be translated into functional protein 19 .”
Structure 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
Hashiba, A., Toyooka, M., Sato, Y., Maeki, M., Tokeshi, M., & Harashima, H. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.08.031 · Cited by 66
Cao, J.-S., Choi, M., Guadagnin, E., Soty, M., Silva, M., Verzieux, V., Weisser, E., Markel, A., Zhuo, J., Liang, S., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23318-2 · Cited by 58
Self-citationLipid‐based nanoparticles as drug delivery systems for cancer immunotherapy
Hao, Y., Ji, Z., Zhou, H., Wu, D., Gu, Z., Wang, D., & ten Dijke, P. (2023) · MedComm · doi:10.1002/mco2.339 · Cited by 71
Bicknell, A. A., Reid, D. W., Licata, M. C., Jones, A. K., Cheng, Y. M., Li, M., Hsiao, C. J., Pepin, C. S., Metkar, M., Levdansky, Y., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114098 · Cited by 68
Fan, Y., Yen, C., Lin, H.-C., Hou, W., Estevez, A., Sarode, A., Goyon, A., Bian, J., Lin, J., Koenig, S. G., et al. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120392 · Cited by 68
Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism
Li, Z., Amaya, L., Pi, R., Wang, S. K., Ranjan, A., Waymouth, R. M., Blish, C. A., Chang, H. Y., & Wender, P. A. (2023) · Nature Communications · doi:10.1038/s41467-023-42672-x · Cited by 65
“While the Jurkat cell line is commonly used as a proxy to evaluate T-cell transfection ef fi cacy due to its easeof access and maintenance, it is still signi fi cantly different from primary T lymphocytes 2,43 , which aremore relevantto clinical applications.”
BackgroundIonizable Lipid Nanoparticle-Mediated Delivery of Plasmid DNA in Cardiomyocytes
Scalzo, S., Santos, A. K., Ferreira, H. A. S., Costa, P. A. C., Prazeres, P. H. D. M., da Silva, N. J. A., Guimarães, L. C., Silva, M. M., Alves, M. T. R., Viana, C. T. R., et al. (2022) · International Journal of Nanomedicine · doi:10.2147/ijn.s366962 · Cited by 64
“52,53 Therefore, it is expected that future studies will yield high safety for other tissues, as well as the heart and liver.”
mRNA-Based Therapeutics in Cancer Treatment
Sun, H., Zhang, Y., Wang, G., Yang, W., & Xu, Y. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020622 · Cited by 65
Bernard, M., Bazin, E., Petiot, N., Lemdani, K., Commandeur, S., Verdelet, C., Margot, S., Perkov, V., Ripoll, M., Garinot, M., et al. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.05.004 · Cited by 63
Influence of ionizable lipid tail length on lipid nanoparticle delivery of mRNA of varying length
Mrksich, K., Padilla, M. S., Joseph, R. A., Han, E. L., Kim, D., Palanki, R., Xu, J., & Mitchell, M. J. (2024) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37705 · Cited by 67
“24 28 Organ tropisms of LNPs are also guided by ILs due to the formation of protein coronas, 29 – 33 targeted delivery to specific cell types, 34,35 and specific uptake pathways.”
Backgroundde Picciotto, S., DeVita, N., Hsiao, C. J., Honan, C., Tse, S., Nguyen, M., Ferrari, J. D., Zheng, W., Wipke, B. T., & Huang, E. (2022) · Nature Communications · doi:10.1038/s41467-022-31130-9 · Cited by 60
Nanomaterials‐Mediated Co‐Stimulation of Toll‐Like Receptors and CD40 for Antitumor Immunity
Yan, J., Zhang, Y., Du, S., Hou, X., Li, W., Zeng, C., Zhang, C., Cheng, J. K. J., Deng, B., McComb, D. W., et al. (2022) · Advanced Materials · doi:10.1002/adma.202207486 · Cited by 61
Activatable NIR‐II Photothermal Lipid Nanoparticles for Improved Messenger RNA Delivery
Li, B., Zhao, M., Lai, W., Zhang, X., Yang, B., Chen, X. S., & Ni, Q. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202302676 · Cited by 61
Baek, R. C., Coughlan, K. A., Jiang, L., Liang, M., Ci, L., Singh, H., Zhang, H., Kaushal, N., Rajlic, I. L., Van, L. M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47460-9 · Cited by 69
“…hPCCA and hPCCB proteins (mRNA-3927), hMUT protein (MMA-3705), or hPAH protein (mRNA-3210) was synthesized in vitro by T7 RNA polymerase – mediated transcription from a linearized DNA template containing the 5 ′ and 3 ′ untranslated regions and a poly(A) tail, as previously described 25,26 .”
Zwitterionic Polymer-Functionalized Lipid Nanoparticles for the Nebulized Delivery of mRNA
Jiang, A. Y., Lathwal, S., Meng, S., Witten, J. J., Beyer, E., McMullen, P., Hu, Y., Manan, R. S., Raji, I. O., Langer, R., et al. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.4c11347 · Cited by 60
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
Intracellular Routing and Recognition of Lipid-Based mRNA Nanoparticles
Delehedde, C., Even, L., Midoux, P., Pichon, C., & Perche, F. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13070945 · Cited by 60
“5% of mRNA was detected in the cytosol after transfection of human epithelial cells with mRNA LNPs made of the ionizable lipid D-LinMC3-DMA [70,71].”
BackgroundInfluentialJoubert, F., Munson, M. J., Sabirsh, A., England, R., Hemmerling, M., Alexander, C., & Ashford, M. B. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.03.011 · Cited by 58
Yang, W., Gadgil, P., Krishnamurthy, V. R., Landis, M. S., Mallick, P., Patel, D., Patel, P. J., Reid, D. L., & Sánchez-Félix, M. (2020) · The AAPS Journal · doi:10.1208/s12248-019-0402-2 · Cited by 62
“In contrast to ASOs, siRNAs would only need to be delivered into the cytosol which can be accomplished with delivery carriers (e.g., lipid nanoparticles, GalNAc conjugates) (100).”
InfluentialBalakrishnan, B., An, D., Nguyen, V., DeAntonis, C. M., Martini, P. G. V., & Lai, K. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.09.018 · Cited by 57
“28 No 1 January 2020 markers including complement and cytokines have been observed in repeat dose toxicology studies conducted in cynomolgus monkeys receiving mRNA encapsulated with a similar LNP (1 mg/kg).(27)”
Application of lipid-based nanoparticles in cancer immunotherapy
Zhang, Z., Yao, S., Hu, Y., Zhao, X. B., & Lee, R. J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.967505 · Cited by 58
Development 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
Messenger RNA-Based Vaccines Against Infectious Diseases
Alameh, M.-G., Weissman, D., & Pardi, N. (2020) · Current Topics in Microbiology and Immunology · doi:10.1007/82_2020_202 · Cited by 96
Olson, K. E., Namminga, K. L., Lu, Y., Thurston, M. J., Schwab, A. D., de Picciotto, S., Tse, S., Walker, W., Iacovelli, J., Small, C. G., et al. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120786 · Cited by 56
Messenger RNA vaccines for cancer immunotherapy: progress promotes promise
Huff, A. L., Jaffee, E. M., & Zaidi, N. (2022) · Journal of Clinical Investigation · doi:10.1172/jci156211 · Cited by 60
Targeted Cancer Immunotherapy: Nanoformulation Engineering and Clinical Translation
Yu, M., Yang, W., Yue, W., & Chen, Y. (2022) · Advanced Science · doi:10.1002/advs.202204335 · Cited by 54
Masarwy, R., Stotsky‐Oterin, L., Elisha, A., Hazan‐Halevy, I., & Peer, D. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115359 · Cited by 59
Jian, F., Wec, A. Z., Feng, L., Yu, Y., Wang, L., Wang, P., Yu, L., Wang, J., Hou, J., Berrueta, D. M., et al. (2025) · Nature Microbiology · doi:10.1038/s41564-025-02030-7 · Cited by 57
“LNP-formulated mRNA was produced through a modified ethanol-drop nanoprecipitation process as described previously 47,50,59–62 .”
Tanaka, H., Sakurai, Y., Anindita, J., & Akita, H. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.07.001 · Cited by 56
Systemic modified messenger RNA for replacement therapy in alpha 1-antitrypsin deficiency
Karadagi, A., Cavedon, A. G., Zemack, H., Nowak, G., Eybye, M. E., Zhu, X., Guadagnin, E., White, R. A., Rice, L. M., Frassetto, A. L., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-64017-0 · Cited by 54
Recent advancements in lipid–mRNA nanoparticles as a treatment option for cancer immunotherapy
Karmacharya, P., Patil, B. R., & Kim, J. O. (2022) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-022-00569-9 · Cited by 54
“L5, an amino lipid, has been shown to have efficient mRNA delivery in rodent and primate models with optimal pharmacokinetics and non-toxic side effects (Sabnis et al. 2018).”
BackgroundLipid nanoparticle-based mRNA candidates elicit potent T cell responses
Zeng, Y., Escalona-Rayo, O., Knol, R. A., Kros, A., & Slütter, B. (2022) · Biomaterials Science · doi:10.1039/d2bm01581a · Cited by 54
Nano-bio interactions in mRNA nanomedicine: Challenges and opportunities for targeted mRNA delivery
Saiding, Q., Zhang, Z., Chen, S., Xiao, F., Chen, Y., Li, Y., Zhen, X., Khan, M. M., Chen, W., Koo, S., et al. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115116 · Cited by 59
Ultrasonic particles: An approach for targeted gene delivery
Walsh, A. P. G., Gordon, H. N., Peter, K., & Wang, X. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113998 · Cited by 58
“Biocompatible, neutral or helper phospholipids have been incorporated in these particles to reduce toxicity [15,70,80,88-91].”
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
Advances in mRNA therapeutics for cancer immunotherapy: From modification to delivery
Han, G., Noh, D., Lee, H., Lee, S., Kim, S., Yoon, H. Y., & Hyeon, L. S. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114973 · Cited by 53
“Moderna has developed a wide range of ionizable lipids, such as Lipid 5, that are less immunostimulatory than MC3 in non-human primates [130, 131].”
Xu, L., Shao, Z., Fang, X., Xin, Z., Zhao, S., Zhang, H., Zhang, Y., Zheng, W., Yu, X., Zhang, Z., et al. (2024) · Exploration · doi:10.1002/exp.20230165 · Cited by 56
Rational Design of Lipid Nanoparticles for Enhanced mRNA Vaccine Delivery via Machine Learning
Bae, S., Choi, H., Lee, J., Kang, M., Ahn, S., Lee, Y., Choi, H., Jo, S., Lee, Y., Park, H., et al. (2024) · Small · doi:10.1002/smll.202405618 · Cited by 55
Kimura, T., Leal, J. M., Simpson, A., Warner, N. L., Berube, B. J., Archer, J. F., Park, S., Kurtz, R., Hinkley, T., Nicholes, K., et al. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.06.017 · Cited by 52
Emerging Concepts of Nanobiotechnology in mRNA Delivery
Wang, Y., & Yu, C. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202003545 · Cited by 54
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
Robust, Durable Gene Activation In Vivo via mRNA-Encoded Activators
Beyersdorf, J. P., Bawage, S. S., Iglesias, N., Peck, H. E., Hobbs, R. A., Wroe, J. A., Zurla, C., Gersbach, C. A., & Santangelo, P. J. (2022) · ACS Nano · doi:10.1021/acsnano.1c10631 · Cited by 52
Chen, Y., Luo, S., Hu, Y., Mao, B., Wang, X., Lu, Z., Shan, Q., Zhang, J., Wang, S., Feng, G., et al. (2024) · Cell · doi:10.1016/j.cell.2024.06.020 · Cited by 50
Modern therapeutic approaches to liver-related disorders
Gardin, A., Remih, K., Gonzales, E. M., Andersson, E. R., & Strnad, P. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2021.12.015 · Cited by 51
The journey of a lifetime — development of Pfizer’s COVID-19 vaccine
Thorn, C. R., Sharma, D., Combs, R. G., Bhujbal, S. V., Romine, J., Zheng, X., Sunasara, K., & Badkar, A. V. (2022) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2022.102803 · Cited by 49
Overcoming biological barriers by virus-like drug particles for drug delivery
Chen, Y., Bao, C., Duan, J., Xie, Y., & Lü, W.-L. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115134 · Cited by 51
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
Tai, W., Yang, K., Liu, Y., Li, R., Feng, S., Chai, B., Zhuang, X., Qi, S., Shi, H., Liu, Z., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43798-8 · Cited by 52
“In contrast, the systemic delivery route may not deliver the administered mRNAs into the tissue of interest and retain the materials in circulation 56,57 .”
BackgroundComprehensive 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
“However, delivery efficiency was lost (Sabnis et al., 2018).”
Nanoscopy for endosomal escape quantification
Andrian, T., Riera, R., Pujals, S., & Albertazzi, L. (2020) · Nanoscale Advances · doi:10.1039/d0na00454e · Cited by 50
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
Nucleic acid-based drugs for patients with solid tumours
Huayamares, S. G., Loughrey, D., Kim, H., Dahlman, J. E., & Sorscher, E. J. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00883-1 · Cited by 54
“High-throughput in vivo screens for the selection of the most effective LNPs or other non-viral nanocarriers, together with evaluations of individual lipid components 97 , can leverage barcoding technologies with reporter payloads to improve functional delivery 91,98 .”
Advances in the design and delivery of RNA vaccines for infectious diseases
Lokras, A. G., Bobak, T. R., Baghel, S. S., Sebastiani, F., & Foged, C. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115419 · Cited by 52
Qin, H., Jiang, Y., Zhang, J., Deng, C., & Zhong, Z. (2019) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.9b00691 · Cited by 49
Ayad, C., Libeau, P., Lacroix, C., Ladavière, C., & Verrier, B. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13030377 · Cited by 48
“In a recent article, Sabnis and her partners from Moderna developed a series of novel amino lipids that improved endosomal escape of mRNA in primates by achieving 2–15% release in the cytosol—depending on the lipid used [40].”
BackgroundDehghani‐Ghahnaviyeh, S., Smith, M., Xia, Y., Dousis, A. D., Grossfield, A. M., & Sur, S. (2023) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.3c01296 · Cited by 47
Meshanni, J. A., Stevenson, E. R., Zhang, D., Sun, R., Ona, N. A., Reagan, E. K., Абрамова, Е. В., Guo, C., Wilkinson, M. L., Baboo, I., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56448-y · Cited by 48
Lu, Z., & Sun, D. (2025) · Pharmaceutical Research · doi:10.1007/s11095-025-03890-8 · Cited by 53
“The branched ionizable lipids also induce more efficient endosomal escape than lamellar lipid MC3 in mRNA LNPs [25, 69].”
Dynamic mRNA polyplexes benefit from bioreducible cleavage sites for in vitro and in vivo transfer
Levačić, A. K., Berger, S., Müller, J., Wegner, A., Lächelt, U., Dohmen, C., Rudolph, C., & Wagner, E. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.09.016 · Cited by 47
mRNA delivery in cancer immunotherapy
Zhong, Y., Du, S., & Dong, Y. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.03.001 · Cited by 49
“For example, Sabnis et al.59 reported a MC3-derived material lipid 5, heptadecan-9-yl 8-((2- hydroxyethyl) (8-(nonyloxy)-8-oxooctyl) amino) octanoate, by substituting MC3 linoleic tail with a new one containing ester lipids.”
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Heuts, J., Jiskoot, W., OSSENDORP, F. A., & van der Maaden, K. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13050596 · Cited by 46
Nanotechnology-enabled immunoengineering approaches to advance therapeutic applications
Chuang, S. T., Conklin, B., Stein, J. B., Pan, G., & Lee, K. (2022) · Nano Convergence · doi:10.1186/s40580-022-00310-0 · Cited by 48
Yi, J., Lei, X., Guo, F., Chen, Q., Chen, X., Zhao, K., Zhu, C., Cheng, X., Lin, J., Yin, H., et al. (2023) · Antiviral Research · doi:10.1016/j.antiviral.2023.105618 · Cited by 45
Jung, O., Jung, H., Thủy, L. T. T., Choi, M., Kim, S., Jeon, H., Yang, J., Kim, S., Kim, T., Lee, E., et al. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202303857 · Cited by 47
Shi, R., Liu, X., Wang, Y., Pan, M., Wang, S., Shi, L., & Ni, B. (2024) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2024.2342592 · Cited by 48
“8,15 mRNA vaccine technology has been applied to a variety of infectious diseases, such as mRNA vaccines are already in clinical studies for the prevention of viruses like HIV-1, chikungunya, Zika, and influenza.”
The dynamic process of mRNA delivery by lipid nanoparticles in vivo
Ma, R., Li, Y., Wei, Y., Zhou, J., Ma, J., Zhang, M., Tu, J., Jiang, J., Xie, S., Tan, W., et al. (2024) · Nano Today · doi:10.1016/j.nantod.2024.102325 · Cited by 46
Lipid nanoparticle (LNP) mediated mRNA delivery in neurodegenerative diseases
Moosavi, S. G., Rahiman, N., Jaafari, M. R., & Arabi, L. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.113641 · Cited by 54
From micro to nano: evolution and impact of drug delivery in treating disease
Hrkach, J., & Langer, R. (2020) · Drug Delivery and Translational Research · doi:10.1007/s13346-020-00769-6 · Cited by 45
The potential of RNA-based therapy for kidney diseases
Bondue, T., van den Heuvel, L. P., Levtchenko, E. N., & Brock, R. E. (2022) · Pediatric Nephrology · doi:10.1007/s00467-021-05352-w · Cited by 49
“While a certain degree of accumulation of this type of LNP in the kidneys has been shown, they mostly direct the cargo towards the liver [64, 65].”
BackgroundNanoparticles in clinical trials of COVID-19: An update
Rauf, A., Abu‐Izneid, T., Khalil, A. A., Hafeez, N., Olatunde, A., Rahman, M. M., Semwal, P., Al-Awthan, Y. S., Bahattab, O. S., Khan, I. N., et al. (2022) · International Journal of Surgery · doi:10.1016/j.ijsu.2022.106818 · Cited by 47
An OX40L mRNA vaccine inhibits the growth of hepatocellular carcinoma
Deng, Z., Yang, H., Tian, Y., Liu, Z., Sun, F., & Yang, P. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.975408 · Cited by 46
Hoecke, L. V., Verbeke, R., Vlieger, D. D., Dewitte, H., Roose, K., Nevel, S. V., Krysko, O., Bachert, C., Schepens, B., Lentacker, I., et al. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.04.015 · Cited by 46
“Therefore, more clinicallyadvanced lipid formulations make use of a new generation of cationic lipids, referred to as ionizable aminolipids.(41,42) The acid dissociation constant (pKa) of these ionizable lipids gives them properties that allow them to form more stable complexes with mRNA at acidic pH, while potential…”
BackgroundThalmayr, S., Grau, M., Peng, L., Pöhmerer, J., Wilk, U., Folda, P., Yazdi, M., Weidinger, E., Burghardt, T., Höhn, M., et al. (2023) · Advanced Materials · doi:10.1002/adma.202211105 · Cited by 45
Understanding Intracellular Biology to Improve mRNA Delivery by Lipid Nanoparticles
Hunter, M. R., Cui, L., Porebski, B. T., Pereira, S. G. T., Sonzini, S., Odunze, U., Iyer, P., Engkvist, O., Lloyd, R. L., Peel, S. E., et al. (2023) · Small Methods · doi:10.1002/smtd.202201695 · Cited by 44
Yamazaki, K., Kubara, K., Ishii, S., Kondo, K., Suzuki, Y., Miyazaki, T., Mitsuhashi, K. O., Ito, M., & Tsukahara, K. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.06.023 · Cited by 44
“Truong et al.32 showed that luciferase protein in the liver was undetectable 72 days after luc-mRNA/LNP. Sabnis et al.42 reported that hEPO induced by a bolus of hEPO-mRNA/LNP almost disappeared from the blood after 48 h in rats and cynomolgus monkeys.”
BackgroundEngineered mRNA Delivery Systems for Biomedical Applications
Wang, J., Zhu, H., Gan, J., Liang, G., Li, L., & Zhao, Y. (2023) · Advanced Materials · doi:10.1002/adma.202308029 · Cited by 46
Lipid Nanoparticle-Based Delivery SystemA Competing Place for mRNA Vaccines
Zhang, X., Li, Y., & Zhou, Z. (2024) · ACS Omega · doi:10.1021/acsomega.3c08353 · Cited by 43
Spatial omics advances for in situ RNA biology
Ren, J., Luo, S., Shi, H., & Wang, X. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.08.002 · Cited by 45
Scope and challenges of nanoparticle-based mRNA delivery in cancer treatment
Karim, M. E., Haque, S. T., Al-Busaidi, H., Bakhtiar, A., Tha, K. K., Holl, M. M. B., & Chowdhury, E. H. (2022) · Archives of Pharmacal Research · doi:10.1007/s12272-022-01418-x · Cited by 45
Nanoscale delivery platforms for RNA therapeutics: Challenges and the current state of the art
Rhym, L. H., & Anderson, D. G. (2022) · Med · doi:10.1016/j.medj.2022.02.001 · Cited by 45
Tanaka, H., Hagiwara, S., Shirane, D., Yamakawa, T., Sato, Y., Matsumoto, C., Ishizaki, K., Hishinuma, M., Chida, K., Sasaki, K., et al. (2023) · ACS Nano · doi:10.1021/acsnano.2c10501 · Cited by 44
Rohde, C. M., Lindemann, C., Giovanelli, M. A., Sellers, R. S., Diekmann, J., Choudhary, S., Ramaiah, L., Vogel, A. B., Chervona, Y., Muik, A., et al. (2023) · Vaccines · doi:10.3390/vaccines11020417 · Cited by 44
“At a physiological pH, the ionizable lipid has a limited positive charge, which reduces clearance by the reticuloendothelial system [59,60], improving the LNP half-life.”
BackgroundGyanani, V., & Goswami, R. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041184 · Cited by 42
“[7] synthesized a series of amino alcohol ionizable lipids.”
BackgroundInfluentialDendritic Cell‐Mimicking Nanoparticles Promote mRNA Delivery to Lymphoid Organs
Cao, Y., Long, J., Sun, H., Miao, Y., Sang, Y., Lü, H., Yu, C., Zhang, Z., Wang, L., Yang, J., et al. (2023) · Advanced Science · doi:10.1002/advs.202302423 · Cited by 41
Therapeutic synthetic and natural materials for immunoengineering
Slezak, A., Chang, K., Hossainy, S., Mansurov, A., Rowan, S. J., Hubbell, J. A., & Guler, M. O. (2024) · Chemical Society Reviews · doi:10.1039/d3cs00805c · Cited by 44
Chaudhary, N., Newby, A. N., Arral, M. L., Yerneni, S. S., LoPresti, S. T., Doerfler, R., Petersen, D. M. S., Montoya, C., Kim, J. S., Fox, B., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2307810121 · Cited by 49
Ramezanpour, M., & Tieleman, D. P. (2022) · Langmuir · doi:10.1021/acs.langmuir.2c00430 · Cited by 44
Rong, J., Liu, T., Yin, X., Shao, M., Zhu, K., Li, B., Wang, S., Zhu, Y., Zhang, S., Yin, L., et al. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-03167-9 · Cited by 45
“Lipid nanoparticles (LNPs) containing an ionizable lipid (DLin‑MC3‑DMA, MC3) are currently among the most advanced oligonucleotide delivery systems [22–24].”
BackgroundOn-patient medical record and mRNA therapeutics using intradermal microneedles
Han, J., Kanelli, M., Liu, Y., Daristotle, J. L., Pardeshi, A., Forster, T. A., Karchin, A., Folk, B., Murmann, L., Tostanoski, L. H., et al. (2025) · Nature Materials · doi:10.1038/s41563-024-02115-4 · Cited by 44
Delivery of synthetic mRNAs for tissue regeneration
Steinle, H., Weber, M., Stoppelkamp, S., Große‐Berkenbusch, K., Golombek, S., Weber, M., Çanak-Ipek, T., Trenz, S.-M., Schlensak, C., & Avci‐Adali, M. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114007 · Cited by 42
CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis
Gillmore, J. D., Gane, E. J., Täubel, J., Kao, J., Fontana, M., Maitland, M. L., Seitzer, J. L., O'Connell, D., Walsh, K. R., Wood, K. M., et al. (2022) · Yearbook of pediatric endocrinology · doi:10.1530/ey.19.14.13 · Cited by 46
Lu, J., Atochina‐Vasserman, E. N., Maurya, D. S., Shalihin, M. I., Zhang, D., Chenna, S. S., Adamson, J., Liu, M., Shah, H. U. R., Shah, H., et al. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics15061572 · Cited by 40
“Four-component lipid nanoparticles (LNPs) [27–29] consisting of ionizable lipids [27,28], phospholipids [29], cholesterol, and a PEG-conjugated lipid [26–28], represent the state-ofthe-art technology employed by BioNTech/Pfizer [16] and Moderna [17] for the production of their mRNA vaccines (Figure 1A).”
BackgroundIncreasing intracellular dNTP levels improves prime editing efficiency
Liu, P., Ponnienselvan, K., Nyalile, T., Oikemus, S., Joynt, A. T., Iyer, S., Kelly, K. L., Guo, D., Kyawe, P. P., Vanderleeden, E., et al. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02405-x · Cited by 45
Wilson, D. R., Rui, Y., Siddiq, K., Routkevitch, D., & Green, J. J. (2019) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.8b00963 · Cited by 40
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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