siRNA-lipid nanoparticles with long-term storage stability facilitate potent gene-silencing in vivo
Abstract
Considerable efforts have been directed towards discovering and developing delivery vehicles for RNA therapeutics. While most studies emphasize the efficacy and safety of these delivery vehicles, few reports conduct a comprehensive assessment of their storage stability, a critical property for practical applications. Here, we report a potent and safe lipid nanoparticle with long-term storage stability. Through chemical synthesis and screening of cationic lipids, a formulation has been identified that enables potent knockdown of hepatocyte proteins in mice upon intravenous administration (siRNA ED50 ~0.02 mg/kg). Toxicity studies revealed that a dose of 2mg/kg was well tolerated in rats, the most sensitive rodent model. We identified that a cyclic chemical structure in cationic lipids improved particle stability. The nanoparticles showed over 1.5 year storage stability as a liquid, with over 90% siRNA encapsulation without any changes in particle size. This novel delivery material has promising potential as a drug product that could bring RNA therapeutics to the treatment of liver-related disorders.
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siRNA-LNPs are stable over 1.5 years at 4 °C.
“Complementary research by Suzuki et al. showed that siRNA-LNPs are stable over the experimental period, i.e. 1.5 years, at 4 °C (Suzuki et al., 2015).”
From mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability (2021) · cites this paper as Suzuki et al., 2015
Cites
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456 · see citing works
Matsumura, Y., & Maeda, H. (1986) · PubMed · Cited by 6,771 · see citing works
Knocking down barriers: advances in siRNA delivery
Whitehead, K. A., Langer, R., & Anderson, D. G. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2742 · Cited by 3,115 · see citing works
Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs
Soutschek, J., Akinc, A., Bramlage, B., Charissé, K., Constien, R., Donoghue, M., Elbashir, S. M., Geick, A., Hadwiger, P., Harborth, J., et al. (2004) · Nature · doi:10.1038/nature03121 · Cited by 2,189 · see citing works
Oligonucleotide-Modified Gold Nanoparticles for Intracellular Gene Regulation
Rosi, N. L., Giljohann, D. A., Thaxton, C. S., Lytton‐Jean, A. K. R., Han, M. S., & Mirkin, C. A. (2006) · Science · doi:10.1126/science.1125559 · Cited by 1,988 · see citing works
Rational design of cationic lipids for siRNA delivery
Semple, S. C., Akinc, A., Chen, J., Sandhu, A. P., Mui, B. L., Cho, C. K., Sah, D. W. Y., Stebbing, D., Crosley, E. J., Yaworski, E., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1602 · Cited by 1,822 · see citing works
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 · see citing works
Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms
Akinc, A., Querbes, W., De, S., Qin, J., Frank-Kamenetsky, M., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Cantley, W. L., Dorkin, J. R., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.85 · Cited by 1,261 · see citing works
A combinatorial library of lipid-like materials for delivery of RNAi therapeutics
Akinc, A., Zumbuehl, A., Goldberg, M. S., Leshchiner, E. S., Busini, V., Hossain, N., Bacallado, S., Nguyen, D. N., Fuller, J. E., Alvarez, R., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1402 · Cited by 1,228 · see citing works
Nair, J. K., Willoughby, J. L. S., Chan, A., Charisse, K., Alam, M. R., Wang, Q., Hoekstra, M., Kandasamy, P., Kel’in, A. V., Milstein, S., et al. (2014) · Journal of the American Chemical Society · doi:10.1021/ja505986a · Cited by 1,141 · see citing works
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 · see citing works
Engineering targeted viral vectors for gene therapy
Waehler, R., Russell, S. J., & Curiel, D. T. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2141 · Cited by 687 · see citing works
In vivo delivery of miRNAs for cancer therapy: Challenges and strategies
Chen, Y., Gao, D.-Y., & Huang, L. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.05.009 · Cited by 681 · see citing works
Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes
Rozema, D. B., Lewis, D. L., Wakefield, D. H., Wong, S. C., Klein, J. J., Roesch, P. L., Bertin, S. L., Reppen, T. W., Chu, Q., Blokhin, A. V., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703778104 · Cited by 658 · see citing works
Maier, 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 · see citing works
Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity
Whitehead, K. A., Dorkin, J. R., Vegas, A. J., Chang, P. H., Veiseh, O., Matthews, J., Fenton, O. S., Zhang, Y., Olejnik, K. T., Yesilyurt, V., et al. (2014) · Nature Communications · doi:10.1038/ncomms5277 · Cited by 615 · see citing works
Fitzgerald, K. J., Frank-Kamenetsky, M. D., Shulga‐Morskaya, S., Liebow, A., Bettencourt, B. R., Sutherland, J. E., Hutabarat, R. M., Clausen, V. A., Karsten, V., Cehelsky, J. E., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61914-5 · Cited by 574 · see citing works
Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids
Heyes, J., Palmer, L., Bremner, K., & MacLachlan, I. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.06.014 · Cited by 572 · see citing works
Mui, B. L., Tam, Y. K., Jayaraman, M., Ansell, S. M., Du, X., Tam, Y. Y. C., Lin, P. J. C., Chen, S., Narayanannair, J. K., Rajeev, K. G., et al. (2013) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2013.66 · Cited by 509 · see citing works
Preclinical and clinical development of siRNA-based therapeutics
Özcan, G., Özpolat, B., Coleman, R. L., Sood, A. K., & Lopez‐Berestein, G. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.01.007 · Cited by 451 · see citing works
Leung, A. K. K., Hafez, I. M., Baoukina, S., Belliveau, N. M., Zhigaltsev, I. V., Afshinmanesh, E., Tieleman, D. P., Hansen, C. L., Hope, M. J., & Cullis, P. R. (2012) · The Journal of Physical Chemistry C · doi:10.1021/jp303267y · Cited by 364 · see citing works
Xu, X., Xie, K., Zhang, X.-Q., Pridgen, E. M., Park, G. Y., Cui, D. S., Shi, J., Wu, J., Kantoff, P. W., Lippard, S. J., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303958110 · Cited by 340 · see citing works
Sato, Y., Hatakeyama, H., Sakurai, Y., Hyodo, M., Akita, H., & Harashima, H. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.09.009 · Cited by 310 · see citing works
Wisse, E., Jacobs, F., Topal, B., Frederik, P. M., & Geest, B. D. (2008) · Gene Therapy · doi:10.1038/gt.2008.60 · Cited by 290 · see citing works
Delivery of therapeutic oligonucleotides with cell penetrating peptides
Boisguérin, P., Deshayes, S., Gait, M. J., O’Donovan, L., Godfrey, C., Betts, C., Wood, M. J. A., & Lebleu, B. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.02.008 · Cited by 245 · see citing works
Cuellar, T. L., Barnes, D., Nelson, C., Tanguay, J., Yu, S., Wen, X., Scales, S. J., Gesch, J., Davis, D., Smith, A. V. B., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1362 · Cited by 215 · see citing works
Safety profile of RNAi nanomedicines
Barros, S. A., & Gollob, J. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.06.007 · Cited by 126 · see citing works
Zhang, J., Fan, H., Levorse, D. A., & Crocker, L. S. (2011) · Langmuir · doi:10.1021/la104590k · Cited by 95 · see citing works
Boal, A. K., & Rotello, V. M. (2000) · Langmuir · doi:10.1021/la0012384 · Cited by 90 · see citing works
Cell-penetrating peptide-conjugated lipid nanoparticles for siRNA delivery
Asai, T., Tsuzuku, T., Takahashi, S., Okamoto, A., Dewa, T., Nango, M., Hyodo, K., Ishihara, H., Kikuchi, H., & Oku, N. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.01.107 · Cited by 84 · see citing works
Gindy, M. E., Feuston, B., Glass, A., Arrington, L., Haas, R. M., Schariter, J., & Stirdivant, S. M. (2014) · Molecular Pharmaceutics · doi:10.1021/mp500367k · Cited by 70 · see citing works
Size-Dependent Knockdown Potential of siRNA-Loaded Cationic Nanohydrogel Particles
Nuhn, L., Tomcin, S., Miyata, K., Mailänder, V., Landfester, K., Kataoka, K., & Zentel, R. (2014) · Biomacromolecules · doi:10.1021/bm501148y · Cited by 68 · see citing works
Wang, Y., & Huang, L. (2013) · Nature Biotechnology · doi:10.1038/nbt.2634 · Cited by 62 · see citing works
Microfluidic-Based Manufacture of siRNA-Lipid Nanoparticles for Therapeutic Applications
Walsh, C., Ou, K., Belliveau, N. M., Leaver, T., Wild, A., Huft, J., Lin, P. J. C., Chen, S., Leung, A. K. K., Lee, J. B., et al. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-0363-4_6 · Cited by 55 · see citing works
Hickerson, R. P., Flores, M. A., Leake, D., Lara, M. F., Contag, C. H., Leachman, S. A., & Kaspar, R. L. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2010.426 · Cited by 54 · see citing works
Zhang, J., Fan, H., Levorse, D. A., & Crocker, L. S. (2011) · Langmuir · doi:10.1021/la201464k · Cited by 48 · see citing works
Prakash, T. P., Lima, W. F., Murray, H. M., Elbashir, S. M., Cantley, W. L., Foster, D., Jayaraman, M., Chappell, A. E., Manoharan, M., Swayze, E. E., et al. (2013) · ACS Chemical Biology · doi:10.1021/cb4001316 · Cited by 48 · see citing works
Gindy, M. E., Leone, A. M., & Cunningham, J. J. (2012) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2012.642363 · Cited by 43 · see citing works
Targeted siRNA Delivery and mRNA Knockdown Mediated by Bispecific Digoxigenin-binding Antibodies
Schneider, B., Grote, M., John, M., Haas, A. K., Bramlage, B., lckenstein, L. M., Jahn‐Hofmann, K., Bauss, F., Cheng, W., Croasdale, R., et al. (2012) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2012.39 · Cited by 42 · see citing works
Tanaka, H., Akita, H., Ishiba, R., Tange, K., Arai, M., Kubo, K., & Harashima, H. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.016 · Cited by 37 · see citing works
Ge, A., Peng, Q., Wu, H., Liu, H., Tong, Y., Nishida, T., Yoshida, N., Suzuki, K., Sakai, T., Osawa, M., et al. (2013) · Langmuir · doi:10.1021/la403502k · Cited by 19 · see citing works
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mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability
Schoenmaker, L., Witzigmann, D., Kulkarni, J. A., Verbeke, R., Kersten, G., Jiskoot, W., & Crommelin, D. J. A. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120586 · Cited by 1,566 · see citing works
Lipids and Lipid Derivatives for RNA Delivery
Zhang, Y., Sun, C., Wang, C., Jankovic, K. E., & Dong, Y. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00244 · Cited by 638 · see citing works
Challenges of Storage and Stability of mRNA-Based COVID-19 Vaccines
Uddin, M. N., & Roni, M. A. (2021) · Vaccines · doi:10.3390/vaccines9091033 · Cited by 371 · see citing works
Suzuki, Y., & Ishihara, H. (2021) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2021.100424 · Cited by 304 · see citing works
Lipid nanoparticles for delivery of messenger RNA to the back of the eye
Patel, S., Ryals, R. C., Weller, K. K., Pennesi, M. E., & Sahay, G. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.04.015 · Cited by 260 · see citing works
Angelova, A., Garamus, V. M., Angelov, B., Tian, Z., Li, Y., & Zou, A. (2017) · Advances in Colloid and Interface Science · doi:10.1016/j.cis.2017.04.006 · Cited by 211 · see citing works
Sato, Y., Hashiba, K., Sasaki, K., Maeki, M., Tokeshi, M., & Harashima, H. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.01.001 · Cited by 180 · see citing works
Research Advances on the Stability of mRNA Vaccines
Cheng, F., Wang, Y., Bai, Y., Liang, Z., Mao, Q., Liu, D., Wu, X., & Xu, M. (2023) · Viruses · doi:10.3390/v15030668 · Cited by 171 · see citing works
Zhang, H., Vandesompele, J., Braeckmans, K., Smedt, S. C. D., & Remaut, K. (2023) · Chemical Society Reviews · doi:10.1039/d3cs00194f · Cited by 140 · see citing works
Biodegradable 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 127 · see citing works
Wu, J., Deng, C., Meng, F., Zhang, J., Sun, H., & Zhong, Z. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.12.024 · Cited by 107 · see citing works
A flexible, thermostable nanostructured lipid carrier platform for RNA vaccine delivery
Gerhardt, A., Voigt, E. A., Archer, M. C., Reed, S., Larson, E., Hoeven, N. V., Kramer, R. M., Fox, C. B., & Casper, C. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.03.009 · Cited by 86 · see citing works
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 85 · see citing works
Sun, P., Huang, W., Jin, M., Wang, Q., Fan, B., Kang, L., & Gao, Z. (2016) · International Journal of Nanomedicine · doi:10.2147/ijn.s105427 · Cited by 84 · see citing works
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 81 · see citing works
Therapeutic Potential of LNP-Mediated Delivery of miR-634 for Cancer Therapy
Gokita, K., Inoue, J., Ishihara, H., Kojima, K., & Inazawa, J. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.10.045 · Cited by 78 · see citing works
Structural analysis of nanoparticulate carriers for encapsulation of macromolecular drugs
Angelov, B., Garamus, V. M., Drechsler, M., & Angelova, A. (2016) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2016.11.064 · Cited by 68 · see citing works
Jia, Z., Gong, Y. Q., Pi, Y., Liu, X., Gao, L., Kang, L., Wang, J., Yang, F., Tang, J., Lu, W., et al. (2017) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.7b00709 · Cited by 67 · see citing works
Suzuki, Y., Hyodo, K., Suzuki, T., Tanaka, Y., Kikuchi, H., & Ishihara, H. (2017) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2017.01.016 · Cited by 64 · see citing works
Suzuki, Y., & Ishihara, H. (2016) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2016.06.124 · Cited by 57 · see citing works
Tanaka, H., Sakurai, Y., Anindita, J., & Akita, H. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.07.001 · Cited by 56 · see citing works
Jakubek, Z. J., Chen, S., Zaifman, J., Tam, Y. Y. C., & Zou, S. (2023) · Langmuir · doi:10.1021/acs.langmuir.2c02657 · Cited by 52 · see citing works
Lipid-based nanocarriers for delivery of small interfering RNA for therapeutic use
Parashar, D., Rajendran, V., Shukla, R., & Sistla, R. (2019) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2019.105159 · Cited by 47 · see citing works
Kubara, K., Yamazaki, K., Miyazaki, T., Kondo, K., Kurotaki, D., Tamura, T., & Suzuki, Y. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.01.020 · Cited by 50 · see citing works
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 46 · see citing works
Nakamura, T., Yamada, Y., Sato, Y., Khalil, I. A., & Harashima, H. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119329 · Cited by 44 · see citing works
Roesch, A., Zölls, S., Stadler, D., Helbig, C., Wuchner, K., Kersten, G. F. A., Hawe, A., Jiskoot, W., & Menzen, T. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2021.12.011 · Cited by 44 · see citing works
Development of in silico methodology for siRNA lipid nanoparticle formulations
Gao, H., Kan, S., Ye, Z., Feng, Y., Jin, L., Zhang, X., Deng, J., Chan, G., Hu, Y., Wang, Y., et al. (2022) · Chemical Engineering Journal · doi:10.1016/j.cej.2022.136310 · Cited by 42 · see citing works
Hirai, Y., Ryoko, S., Song, F., Koide, H., Naofumi, F., Tomita, K., Maeda, N., Oku, N., & Asai, T. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.119479 · Cited by 41 · see citing works
Why mRNA-ionizable LNPs formulations are so short-lived: causes and way-out
De, A., & Ko, Y. T. (2023) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2023.2162876 · Cited by 36 · see citing works
Ayat, N. R., Sun, Z., Sun, D., Yin, M., Hall, R. C., Vaidya, A. M., Liu, X., Schilb, A. L., Scheidt, J. H., & Lu, Z.-R. (2019) · Nucleic Acid Therapeutics · doi:10.1089/nat.2019.0784 · Cited by 33 · see citing works
Li, L., Foley, J. P., & Helmy, R. (2019) · Journal of Chromatography A · doi:10.1016/j.chroma.2019.04.061 · Cited by 33 · see citing works
Sato, S., Sano, S., Muto, H., Kubara, K., Kondo, K., Miyazaki, T., Suzuki, Y., Uemoto, Y., & Ukai, K. (2024) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.c24-00089 · Cited by 34 · see citing works
Cytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles
Hirai, Y., Hirose, H., Imanishi, M., Asai, T., & Futaki, S. (2021) · Scientific Reports · doi:10.1038/s41598-021-99180-5 · Cited by 28 · see citing works
Pizzuto, M., Gangloff, M., Scherman, D., Gay, N. J., Escriou, V., Ruysschaert, J., & Lonez, C. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.12.029 · Cited by 26 · see citing works
De, A., & Ko, Y. T. (2022) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2023.2153832 · Cited by 23 · see citing works
Irf5 siRNA-loaded biodegradable lipid nanoparticles ameliorate concanavalin A-induced liver injury
Kawase, W., Kurotaki, D., Suzuki, Y., Ishihara, H., Ban, T., Sato, G. R., Ichikawa, J., Yanai, H., Taniguchi, T., Tsukahara, K., et al. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.08.023 · Cited by 22 · see citing works
Zimmermann, C. M., Deßloch, L., Jürgens, D. C., Luciani, P., & Merkel, O. M. (2023) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2023.11.007 · Cited by 21 · see citing works
石郷岡秀俊, Katsumata, H., Saiga, K., Tokita, D., Motoi, S., Matsui, C., Suzuki, Y., Tomimatsu, A., Nakatani, T., Kuboi, Y., et al. (2022) · Transplantation · doi:10.1097/tp.0000000000004207 · Cited by 20 · see citing works
Suzuki, Y., Katsurada, Y., & Hyodo, K. (2023) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.3c00547 · Cited by 21 · see citing works
Simplifying the Chemical Structure of Cationic Lipids for siRNA-Lipid Nanoparticles
Kuboyama, T., Yagi, K., Naoi, T., Era, T., Yagi, N., Nakasato, Y., Yabuuchi, H., Takahashi, S., Shinohara, F., Iwai, H., et al. (2019) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.8b00652 · Cited by 19 · see citing works
Li, Y., Wang, X., Zeng, X., Ren, W., Liao, P., & Zhu, B. (2023) · mLife · doi:10.1002/mlf2.12085 · Cited by 16 · see citing works
NANOSPRESSO: toward personalized, locally produced nucleic acid nanomedicines
Sentí, M. E., Ceccaldi, A., Luciani, M., Saber, N., Schürmann, P. J. L., Geerlings, M. W., Hölig, P., de Beer, J., Hannus, M., Campbell, F., et al. (2025) · Frontiers in Science · doi:10.3389/fsci.2025.1458636 · Cited by 17 · see citing works
Muto, H., Kubara, K., Hitaoka, S., Osada, Y., & Suzuki, Y. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.114055 · Cited by 17 · see citing works
Greco, C. T., Andrechak, J. C., Epps, T. H. I., & Sullivan, M. O. (2017) · Biomacromolecules · doi:10.1021/acs.biomac.7b00265 · Cited by 16 · see citing works
Ahmed, T. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16336 · Cited by 16 · see citing works
Tanaka, H., Sato, Y., Harashima, H., & Akita, H. (2016) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2016.1154531 · Cited by 14 · see citing works
De, A., & Ko, Y. T. (2022) · Drug Delivery · doi:10.1080/10717544.2022.2108523 · Cited by 13 · see citing works
Immune-Modulating Lipid Nanomaterials for the Delivery of Biopharmaceuticals
Kim, S., Choi, B., Kim, Y., & Shim, G. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15061760 · Cited by 13 · see citing works
RNA Modifications in Gastrointestinal Cancer: Current Status and Future Perspectives
Zhang, X., Su, H., Chen, H., Li, Q., Liu, X., Zhang, L., Wu, W. K. K., Chan, M. T. V., & Chen, H. (2022) · Biomedicines · doi:10.3390/biomedicines10081918 · Cited by 13 · see citing works
Kuboi, Y., Suzuki, Y., Motoi, S., Matsui, C., Toritsuka, N., Nakatani, T., Tahara, K., Takahashi, Y., Ida, Y., Tomimatsu, A., et al. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.01.005 · Cited by 12 · see citing works
Capillary electrophoresis method to determine siRNA complexation with cationic liposomes
Furst, T., Bettonville, V., Farcaş, E., Frère, A., Lechanteur, A., Évrard, B., Fillet, M., Piel, G., & Servais, A. (2016) · Electrophoresis · doi:10.1002/elps.201600249 · Cited by 11 · see citing works
De, A., Kang, J. H., Sauraj, Lee, O. H., & Ko, Y. T. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.130783 · Cited by 9 · see citing works
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Lahan, M., Saikia, T., Baishya, R., Bharali, A., Baruah, S., Ghose, S., Biswas, N., Laloo, D., Medhi, S., & Sahu, B. P. (2025) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2025.102361 · Cited by 1 · see citing works
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Jackson, N. A. C. (2022) · RNA technologies · doi:10.1007/978-3-031-08415-7_2
Becker, J., Barbieri, B. D., Shattock, R. J., & Becer, C. R. (2026) · Chemical Science · doi:10.1039/d6sc03833f
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Adzavon, K. P., Zhao, W., & Sheng, W. (2026) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2026.127405
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Abuhassan, Q., Aldulaimi, A., Waleed, O. S., Ganesan, S., Kavitha, V., Maharana, L., Sharma, R., Latipova, M., Madatova, N., Jumanazarov, D., et al. (2026) · Bioimpacts · doi:10.34172/bi.33056
- Authors
- Suzuki, Y., Hyodo, K., Tanaka, Y., & Ishihara, H.
- Affiliations
- Eisai (Japan) (JP)
- SOGO Pharmaceutical Co., Ltd. (Japan) (JP)
- Corresponding author
- Suzuki, Y.
- ORCID
- Suzuki, Y.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 220
- Issue
- Pt A
- Pages
- 44-50
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2114387194
- Cited by
- 71
- References
- 41
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 7 · 2023: 11 · 2022: 9 · 2021: 7 · 2020: 2 · 2019: 8 · 2018: 1 · 2017: 4 · 2016: 7
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (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
- storage stability, cationic lipids, gene silencing, intravenous administration, nanoparticle toxicity, siRNA encapsulation, liver disease
- MeSH terms
- Animals, Lipids, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Time Factors, Gene Silencing, RNA, Small Interfering, Mice, Nanoparticles
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