In Vivo Introduction of mRNA Encapsulated in Lipid Nanoparticles to Brain Neuronal Cells and Astrocytes via Intracerebroventricular Administration
Abstract
Gene therapy is a promising strategy for curing certain types of brain diseases. Supplementation of therapeutic proteins such as aromatic amino acid decarboxylase (AADC) or nerve growth factor (NGF) have been reported to be successful examples of such treatments. However, there are safety concerns because these systems are based on virus-based gene vectors. A safe and efficient artificial carrier is thus urgently needed as an alternative. In this study, an mRNA based artificial gene carrier was introduced into the mouse brain via intracerebroventricular administration. As a carrier, a lipid nanoparticle (LNP) composed of environmentally sensitive lipid-like materials called an SS-cleavable proton-activated lipid-like material is used. The apolipoprotein E mediated cellular uptake of the lipid nanoparticles is one of the key features for its superior and homogeneous transfection activity compared to commercially available transfection reagents in both in vitro and in vivo situations. Immunostaining of brain specimens suggested that exogenous proteins can be introduced into neuronal cells as well as astrocytes using the mRNA-based gene carrier. This cannot be achieved using DNA-based artificial gene carriers. The findings suggest that a combination of an mRNA and a lipid based delivery system have great promise as a platform for the treatment of brain disorders.
Integrity signals
Registry
Cites
Statistics
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?
After ICV LNP mRNA delivery, transfected cells appeared localized to restricted brain regions, primarily the cells lining the ventricle wall, with small levels of transfection in brain tissue.
“However, transfected cells appeared to be localized to the restricted brain regions, primarily to the cells lining the ventricle wall, with small levels of transfection in the brain tissue.”
From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [6]
LNPs can deliver eGFP mRNA into neurons and astrocytes after ICV injections.
“Tanaka et al. (2018) demonstrated that LNPs can deliver eGFP mRNA into neurons and astrocytes post-ICV injections (6).”
From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [6]
LNP mRNA complexes have excellent biocompatibility and can transfect a variety of tissues and organs.
“LNP mRNA complexes have excellent biocompatibility and can transfect a variety of tissues and organs (5–9).”
From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [6]
mRNA can be delivered using LNPs after ICV injection into mouse brain tissue.
“Further studies by Tanaka et al. (2018) and Li et al. (2020) demonstrated that mRNA can also be delivered using LNPs after ICV injection into mouse brain tissue (6, 7).”
From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [6]
Cites
Schafer, F. Q., & Buettner, G. R. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00480-4 · Cited by 4,587 · see citing works
Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes
Foust, K. D., Nurre, E., Montgomery, C. L., Hernandez, A., Chan, C. M., & Kaspar, B. K. (2009) · Nature Biotechnology · doi:10.1038/nbt.1515 · Cited by 1,456 · see citing works
Shibata, M., Yamada, S., Kumar, S. R., Calero, M., Bading, J., Frangione, B., Holtzman, D. M., Miller, C. A., Strickland, D. K., Ghiso, J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10498 · Cited by 1,413 · see citing works
Adeno-Associated Virus (AAV) as a Vector for Gene Therapy
Naso, M. F., Tomkowicz, B., Perry, W. L., & Strohl, W. R. (2017) · BioDrugs · doi:10.1007/s40259-017-0234-5 · Cited by 1,362 · 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
Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy
Bu, G. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2620 · Cited by 1,168 · see citing works
Kauffman, K. J., Dorkin, J. R., Yang, J. H., Heartlein, M. W., DeRosa, F., Mir, F. F., Fenton, O. S., & Anderson, D. G. (2015) · Nano Letters · doi:10.1021/acs.nanolett.5b02497 · Cited by 785 · see citing works
apoE isoform–specific disruption of amyloid β peptide clearance from mouse brain
Deane, R., Sagare, A., Hamm, K., Parisi, M., Lane, S., Finn, M. B., Holtzman, D. M., & Zlokovic, B. V. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36663 · Cited by 771 · see citing works
Expression of therapeutic proteins after delivery of chemically modified mRNA in mice
Kormann, M. S. D., Hasenpusch, G., Aneja, M. K., Nica, G., Flemmer, A. W., Herber-Jonat, S., Huppmann, M., Mays, L. E., Illenyi, M., Schams, A., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1733 · Cited by 733 · see citing works
Recognition of Endogenous Nucleic Acids by the Innate Immune System
Roers, A., Hiller, B., & Hornung, V. (2016) · Immunity · doi:10.1016/j.immuni.2016.04.002 · Cited by 541 · see citing works
Miller, J. B., Zhang, S., Kos, P., Xiong, H., Zhou, K., Perelman, S. S., Zhu, H., & Siegwart, D. J. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201610209 · Cited by 540 · see citing works
Thess, A., Grund, S., Mui, B. L., Hope, M. J., Baumhof, P., Fotin-Mleczek, M., & Schlake, T. (2015) · Molecular Therapy · doi:10.1038/mt.2015.103 · Cited by 513 · see citing works
Safety and tolerability of putaminal <i>AADC</i> gene therapy for Parkinson disease
Christine, C. W., Starr, P. A., Larson, P. S., Eberling, J. L., Jagust, W. J., Hawkins, R. A., VanBrocklin, H. F., Wright, J. F., Bankiewicz, K. S., & Aminoff, M. J. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c29356 · Cited by 445 · see citing works
Materials for non-viral intracellular delivery of messenger RNA therapeutics
Kauffman, K. J., Webber, M. J., & Anderson, D. G. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.12.032 · Cited by 400 · see citing works
CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington’s disease
Yang, S., Chang, R., Yang, H., Zhao, T., Hong, Y., Kong, H. E., Sun, X., Qin, Z. S., Jin, P., Li, S., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92087 · Cited by 400 · see citing works
Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems
Guan, S., & Rosenecker, J. (2017) · Gene Therapy · doi:10.1038/gt.2017.5 · Cited by 389 · see citing works
A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson’s disease
Muramatsu, S.-I., Fujimoto, K.-I., Kato, S., Mizukami, H., Asari, S., Ikeguchi, K., Kawakami, T., Urabe, M., Kume, A., Sato, T., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.135 · Cited by 344 · see citing works
Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging
Yang, J. J. J., Chen, H., Vlahov, I. R., Cheng, J., & Low, P. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601455103 · Cited by 317 · see citing works
Long-Term Evaluation of a Phase 1 Study of AADC Gene Therapy for Parkinson's Disease
Mittermeyer, G., Christine, C. W., Rosenbluth, K. H., Baker, S. L., Starr, P. A., Larson, P., Kaplan, P. L., Forsayeth, J., Aminoff, M. J., & Bankiewicz, K. S. (2012) · Human Gene Therapy · doi:10.1089/hum.2011.220 · Cited by 297 · see citing works
Glycaemic control boosts glucosylated nanocarrier crossing the BBB into the brain
Anraku, Y., Kuwahara, H., Fukusato, Y., Mizoguchi, A., Ishii, T., Nitta, K., Matsumoto, Y., Toh, K., Miyata, K., Uchida, S., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00952-3 · Cited by 295 · see citing works
Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease
Tuszynski, M. H., Yang, J. H., Barba, D., U, H.-S., Bakay, R. A. E., Pay, M. M., Masliah, E., Conner, J. M., Kobalka, P., Roy, S., et al. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.1807 · Cited by 287 · see citing works
An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo
Li, B., Luo, X., Deng, B., Wang, J., McComb, D. W., Shi, Y., Gaensler, K. M. L., Tan, X., Dunn, A. L., Kerlin, B. A., et al. (2015) · Nano Letters · doi:10.1021/acs.nanolett.5b03528 · Cited by 261 · see citing works
Wong, L., Goodhead, L., Prat, C. M. A., Mitrophanous, K. A., Kingsman, S. M., & Mazarakis, N. D. (2006) · Human Gene Therapy · doi:10.1089/hum.2006.17.1 · Cited by 184 · see citing works
Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain
Rungta, R. L., Choi, H. B., Lin, P. J., Ko, R. W., Ashby, D., Nair, J., Manoharan, M., Cullis, P. R., & MacVicar, B. A. (2013) · Molecular Therapy—Nucleic Acids · doi:10.1038/mtna.2013.65 · Cited by 165 · see citing works
Uchida, H., Itaka, K., Nomoto, T., Ishii, T., Suma, T., Ikegami, M., Miyata, K., Oba, M., Nishiyama, N., & Kataoka, K. (2014) · Journal of the American Chemical Society · doi:10.1021/ja506194z · Cited by 147 · see citing works
Adeno-Associated Virus Vectors and Neurological Gene Therapy
Ojala, D. S., Amara, D. P., & Schaffer, D. V. (2014) · The Neuroscientist · doi:10.1177/1073858414521870 · Cited by 137 · see citing works
The role of apolipoprotein E in the elimination of liposomes from blood by hepatocytes in the mouse
Yan, X., Kuipers, F., Havekes, L. M., Havinga, R., Dontje, B., Poelstra, K., Scherphof, G. L., & Kamps, J. A. A. M. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.12.137 · Cited by 133 · see citing works
Merkel, S. F., Andrews, A. M., Lutton, E. M., Mu, D., Hudry, E., Hyman, B. T., Maguire, C. A., & Ramirez, S. H. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.13861 · Cited by 132 · see citing works
Masotti, A., Mossa, G., Cametti, C., Ortaggi, G., Bianco, A., Grosso, N. D., Malizia, D., & Esposito, C. (2008) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2008.09.017 · Cited by 130 · see citing works
Hama, S., Akita, H., Iida, S., Mizuguchi, H., & Harashima, H. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkl1165 · Cited by 111 · see citing works
Self-citationBiodegradable Amino-Ester Nanomaterials for Cas9 mRNA Delivery in Vitro and in Vivo
Zhang, X., Li, B., Luo, X., Zhao, W., Jiang, J., Zhang, C., Gao, M., Chen, X., & Dong, Y. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b08163 · Cited by 107 · see citing works
Szebeni, J., Bedöcs, P., Urbanics, R., Bünger, R., Rosivall, L., Tóth, M., & Barenholz, Y. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.02.029 · Cited by 98 · see citing works
Akita, H., Ishiba, R., Hatakeyama, H., Tanaka, H., Sato, Y., Tange, K., Arai, M., Kubo, K., & Harashima, H. (2013) · Advanced Healthcare Materials · doi:10.1002/adhm.201200431 · Cited by 83 · see citing works
Self-citationDetermining the cytotoxicity of catanionic surfactant mixtures on HeLa cells
Vlachy, N., Touraud, D., Heilmann, J., & Kunz, W. (2009) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2008.12.038 · Cited by 81 · see citing works
Lipid Metabolism and Glial Lipoproteins in the Central Nervous System
Hayashi, H. (2011) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.34.453 · Cited by 80 · see citing works
Viral and Synthetic RNA Vector Technologies and Applications
Schott, J. W., Morgan, M., Galla, M., & Schambach, A. (2016) · Molecular Therapy · doi:10.1038/mt.2016.143 · Cited by 76 · see citing works
Jackman, J. A., Mészáros, T., Fülöp, T., Urbanics, R., Szebeni, J., & Cho, N. (2016) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2015.12.377 · Cited by 64 · see citing works
Akita, H., Tamaru, M., Kajimoto, K., Sato, Y., Hatakeyama, H., Harashima, H., & Nakatani, T. (2014) · International Journal of Nanomedicine · doi:10.2147/ijn.s65402 · Cited by 55 · see citing works
Self-citationAkita, H., Noguchi, Y., Hatakeyama, H., Sato, Y., Tange, K., Nakai, Y., & Harashima, H. (2015) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.5b00203 · Cited by 53 · see citing works
Self-citationUkawa, M., Akita, H., Hayashi, Y., Ishiba, R., Tange, K., Arai, M., Kubo, K., Higuchi, Y., Shimizu, K., Konishi, S., et al. (2014) · Advanced Healthcare Materials · doi:10.1002/adhm.201300629 · Cited by 42 · see citing works
Self-citationTanaka, 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
Self-citationAkita, H., Nakatani, T., Kuroki, K., Maenaka, K., Tange, K., Nakai, Y., & Harashima, H. (2015) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2015.05.043 · Cited by 30 · see citing works
Self-citationTanaka, H., Oasa, S., Kinjo, M., Tange, K., Nakai, Y., Harashima, H., & Akita, H. (2016) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2016.11.020 · Cited by 16 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Chemistry of Lipid Nanoparticles for RNA Delivery
Eygeris, Y., Gupta, M., Kim, J., & Sahay, G. (2021) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00544 · Cited by 903 · see citing works
mRNA-based therapeutics: powerful and versatile tools to combat diseases
Qin, S., Tang, X., Chen, Y., Chen, K., Fan, N., Xiao, W., Zheng, Q., Li, G., Teng, Y., Wu, M., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01007-w · Cited by 801 · see citing works
Lipid nanoparticles for nucleic acid delivery: Current perspectives
Samaridou, E., Heyes, J. A., & Lutwyche, P. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.06.002 · Cited by 593 · see citing works
The challenge and prospect of mRNA therapeutics landscape
Weng, Y., Li, C., Yang, T., Hu, B., Zhang, M., Guo, S., Xiao, H., Liang, X.-J., & Huang, Y. (2020) · Biotechnology Advances · doi:10.1016/j.biotechadv.2020.107534 · Cited by 417 · see citing works
Gene therapy for neurodegenerative disorders: advances, insights and prospects
Chen, W., Hu, Y., & Ju, D. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.01.015 · Cited by 191 · see citing works
Loughrey, D., & Dahlman, J. E. (2022) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00601 · Cited by 173 · see citing works
RNA-based scaffolds for bone regeneration: application and mechanisms of mRNA, miRNA and siRNA
Leng, Q., Chen, L., & Lv, Y. (2020) · Theranostics · doi:10.7150/thno.42640 · Cited by 146 · see citing works
Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain
Ogawa, K., Kato, N., Yoshida, M., Hiu, T., Matsuo, T., Mizukami, S., Omata, D., Suzuki, R., Maruyama, K., Mukai, H., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.05.042 · Cited by 144 · see citing works
Lipid Nanoparticles Optimized for Targeting and Release of Nucleic Acid
Jia, Y., Wang, X., Li, L., Li, F., Zhang, J., & Liang, X. (2023) · Advanced Materials · doi:10.1002/adma.202305300 · Cited by 141 · see citing works
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 133 · see citing works
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 · see citing works
Nucleic acid drug vectors for diagnosis and treatment of brain diseases
Lü, Z., Shen, J., Yang, H. J., Wang, J., Zhao, R., Zhang, T.-L., Guo, J. R., & Zhang, X. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01298-z · Cited by 108 · see citing works
Lofts, A., Abu-Hijleh, F. A., Rigg, N., Mishra, R. K., & Hoare, T. R. (2022) · CNS Drugs · doi:10.1007/s40263-022-00930-4 · Cited by 108 · see citing works
Lipid nanoparticle chemistry determines how nucleoside base modifications alter mRNA delivery
Melamed, J. R., Hajj, K. A., Chaudhary, N., Strelkova, D., Arral, M. L., Pardi, N., Alameh, M., Miller, J. B., Farbiak, L., Siegwart, D. J., et al. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.11.022 · Cited by 98 · see citing works
Tateshita, N., Miura, N., Tanaka, H., Masuda, T., Ohtsuki, S., Tange, K., Nakai, Y., Yoshioka, H., & Akita, H. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.08.002 · Cited by 96 · see citing works
Self-citationKim, H. J., Ogura, S., Otabe, T., Kamegawa, R., Sato, M., Kataoka, K., & Miyata, K. (2019) · ACS Central Science · doi:10.1021/acscentsci.9b00843 · Cited by 91 · see citing works
Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?
Moulson, A. J., Squair, J. W., Franklin, R. J. M., Tetzlaff, W., & Assinck, P. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.703810 · Cited by 90 · see citing works
Li, X., Qi, J., Wang, J., Hu, W., Zhou, W., Wang, Y., & Li, T. (2024) · Theranostics · doi:10.7150/thno.84291 · Cited by 96 · see citing works
Uchida, S., & Kataoka, K. (2019) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.36614 · Cited by 90 · see citing works
Luo, M., Lee, L. K. C., Peng, B., Choi, C. H. J., Tong, W. Y., & Voelcker, N. H. (2022) · Advanced Science · doi:10.1002/advs.202201740 · Cited by 81 · see citing works
Ralvenius, W. T., Andresen, J. L., Huston, M. M., Penney, J., Bonner, J. M., Fenton, O. S., Langer, R., & Tsai, L. (2024) · Advanced Materials · doi:10.1002/adma.202309225 · Cited by 78 · see citing works
Astrocytes: Emerging Therapeutic Targets in Neurological Disorders
Valori, C. F., Guidotti, G., Brambilla, L., & Rossi, D. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.04.010 · Cited by 76 · see citing works
Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection
Tuma, J., Chen, Y.-J., Collins, M. G., Paul, A., Li, J., Han, H., Sharma, R., Murthy, N., & Lee, H. Y. (2023) · Biochemistry · doi:10.1021/acs.biochem.3c00371 · Cited by 65 · see citing works
Yoshinaga, N., Uchida, S., Naito, M., Osada, K., Cabral, H., & Kataoka, K. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.01.023 · Cited by 59 · see citing works
High‐Precision Synthesis of RNA‐Loaded Lipid Nanoparticles for Biomedical Applications
Seo, H., Jeon, L., Kwon, J., & Lee, H. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202203033 · Cited by 51 · see citing works
mRNA vaccines in the context of cancer treatment: from concept to application
Fu, Q., Zhao, X., Hu, J., Jiao, Y., Yan, Y., Pan, X., Wang, X., & Jiao, F. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-024-06033-6 · Cited by 53 · see citing works
D’souza, A. A., Nozohouri, S., Bleier, B. S., & Amiji, M. M. (2022) · Pharmaceutical Research · doi:10.1007/s11095-022-03433-5 · Cited by 47 · see citing works
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 52 · see citing works
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 41 · see citing works
Yang, J., Luly, K. M., & Green, J. J. (2023) · WIREs Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1853 · Cited by 40 · see citing works
Lipid-based nanoparticles and RNA as innovative neuro-therapeutics
Tsakiri, M., Zivko, C., Demetzos, C., & Mahairaki, V. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.900610 · Cited by 39 · see citing works
Challenges and Opportunities of Targeting Astrocytes to Halt Neurodegenerative Disorders
Valori, C. F., Possenti, A., Brambilla, L., & Rossi, D. (2021) · Cells · doi:10.3390/cells10082019 · Cited by 37 · see citing works
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 · see citing works
Self-citationNanoparticle Targeting with Antibodies in the Central Nervous System
Lee, J.-H., Chapman, D. V., & Saltzman, W. M. (2023) · BME Frontiers · doi:10.34133/bmef.0012 · Cited by 33 · see citing works
Li, Y., Liu, L., Ji, W., Peng, H., Zhao, R., & Zhang, X. (2020) · Nano Today · doi:10.1016/j.nantod.2020.101006 · Cited by 33 · see citing works
mRNA-based modalities for infectious disease management
Zhang, M., Hussain, A., Yang, H., Zhang, J., Liang, X., & Huang, Y. (2022) · Nano Research · doi:10.1007/s12274-022-4627-5 · Cited by 33 · see citing works
Cho, R., Sakurai, Y., Jones, H. S., Akita, H., Hisaka, A., & Hatakeyama, H. (2020) · Cancers · doi:10.3390/cancers12123630 · Cited by 30 · see citing works
Self-citationAn Overview of Nanomedicines for Neuron Targeting
García-Chica, J., Paraiso, W. K. D., Tanabe, S., Serra, D., Herrero, L., Casals, N., García, J., Ariza, X., Quader, S., & Rodríguez‐Rodríguez, R. (2020) · Nanomedicine · doi:10.2217/nnm-2020-0088 · Cited by 28 · see citing works
Ohto, T., Konishi, M., Tanaka, H., Onomoto, K., Yoneyama, M., Nakai, Y., Tange, K., Yoshioka, H., & Akita, H. (2019) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b18-00783 · Cited by 29 · see citing works
Self-citationMiwa, T., Saito, H., & Akita, H. (2021) · Experimental Brain Research · doi:10.1007/s00221-020-05970-0 · Cited by 26 · see citing works
Self-citationGeng, L., Kato, N., Kodama, Y., Mukai, H., & Kawakami, S. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.122896 · Cited by 27 · see citing works
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 · see citing works
Lipid nanoparticles deliver mRNA to the blood–brain barrier
Kuzminich, Y., Shakked, A., Calkins, R., Rudden, S., Jones, C., Doan, J., Jang, B., Echeverri, E. S., Zenhausern, R., Lian, L., et al. (2024) · Nano Research · doi:10.1007/s12274-024-6827-7 · Cited by 23 · see citing works
Kurimoto, S., Yoshinaga, N., Igarashi, K., Matsumoto, Y., Cabral, H., & Uchida, S. (2019) · Molecules · doi:10.3390/molecules24071303 · Cited by 23 · see citing works
Cell type-targeting nanoparticles in treating central nervous system diseases: Challenges and hopes
Guo, S., & Yi, C. (2023) · Nanotechnology Reviews · doi:10.1515/ntrev-2023-0158 · Cited by 22 · see citing works
Material Design for Next-Generation mRNA Vaccines Using Lipid Nanoparticles
Higuchi, A., Sung, T., Wang, T., Ling, Q., Kumar, S. S., Hsu, S.-T., & Umezawa, A. (2022) · Journal of macromolecular science. Part C, Reviews in macromolecular chemistry and physics/Journal of macromolecular science. Reviews in macromolecular chemistry and physics · doi:10.1080/15583724.2022.2106490 · Cited by 20 · see citing works
Unleashing the potential of mRNA therapeutics for inherited neurological diseases
Monfrini, E., Baso, G., Ronchi, D., Meneri, M., Gagliardi, D., Quetti, L., Verde, F., Ticozzi, N., Ratti, A., Fonzo, A. D., et al. (2024) · Brain · doi:10.1093/brain/awae135 · Cited by 19 · see citing works
Current knowledge on the tissue distribution of mRNA nanocarriers for therapeutic protein expression
Zadory, M., Lopez, E., Babity, S., Gravel, S., & Brambilla, D. (2022) · Biomaterials Science · doi:10.1039/d2bm00859a · Cited by 18 · see citing works
Lipid nanoparticle-mediated delivery of microRNA-124 reduces neuroinflammation
Ma, Z., Dang, H. A., Yang, J., Rodella, G., Mwema, A., Lombaerde, E. D., Chen, Y., Geest, B. G. D., Pesch, V. V., Muccioli, G. G., et al. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123589 · Cited by 19 · see citing works
TDP-43 and NEAT long non-coding RNA: Roles in neurodegenerative disease
Sekar, D., Tusubira, D., & Ross, K. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.954912 · Cited by 18 · see citing works
Nucleic acid delivery by lipid nanoparticles for organ targeting
Guo, J., Gu, M., Chen, Y., Xiong, T., Zhang, Y., Chen, S., Li, M., Chen, X., & Peng, X. (2025) · Chinese Chemical Letters · doi:10.1016/j.cclet.2025.110849 · Cited by 18 · see citing works
Sakurai, Y., Watanabe, H., Nishio, K., Hashimoto, K., Harada, A., Gomi, M., Suzuki, M., Oyama, R., Handa, T., Sato, R., et al. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14081560 · Cited by 17 · see citing works
Self-citationIonizable nanoemulsions for RNA delivery into the central nervous system – importance of diffusivity
Borrajo, M. L., Quijano, A., Lapuhs, P., Rodriguez-Perez, A. I., Anthiya, S., Labandeira-García, J. L., Valenzuela, R., & Alonso, M. J. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.06.051 · Cited by 17 · see citing works
Mohammed, O. A., Elballal, M. S., El-Husseiny, A. A., Khidr, E. G., Tabaa, M. M. E., Elazazy, O. E., Abd‐Elmawla, M. A., Elesawy, A. E., Ibrahim, H. M., Abulsoud, A. I., et al. (2023) · Pathology - Research and Practice · doi:10.1016/j.prp.2023.155023 · Cited by 16 · see citing works
Truong, L. B., Medina-Cruz, D., & Mostafavi, E. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.125185 · Cited by 14 · see citing works
Leveraging high-throughput screening technologies in targeted mRNA delivery
Zhang, Y., Gao, Z., Yang, X. Q., Xu, Q., & Lu, Y. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101101 · Cited by 14 · see citing works
The Astrogenic Balance in the Aging Brain
Andromidas, F., Atashpanjeh, S., Myers, A. J., MacKinnon, B., Shaffer, M. M., & Koob, A. O. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210420095118 · Cited by 13 · see citing works
Wang, S., Guo, B., Wang, H., & Yang, F. (2024) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2024.105547 · Cited by 13 · see citing works
Vío, V., Riveros, A. L., Tapia-Bustos, A., Lespay‐Rebolledo, C., Pérez-Lobos, R., Muñoz, L., Pismante, P., Morales, P., Araya, E., Hassan, N., et al. (2018) · International Journal of Nanomedicine · doi:10.2147/ijn.s175076 · Cited by 13 · see citing works
Cheng, Y., Xu, M., Wu, J., Qian, K., Yang, P., Zhou, L., Meng, R., Li, Y., Wang, T., Sheng, D., et al. (2024) · ACS Nano · doi:10.1021/acsnano.4c09996 · Cited by 12 · see citing works
Manicum, A.-L. E., Sargazi, S., Razzaq, S., Kumar, G. V., Rahdar, A., Zeybekler, S. E., Ain, Q. U., Bilal, M., & Aboudzadeh, M. A. (2022) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2022.103288 · Cited by 9 · see citing works
Therapeutic nucleic acids in regenerative medicine and tissue repair
Saiding, Q., Qin, D., An, S., Patel, D. N., Khan, M. M., Kong, N., & Tao, W. (2024) · Nano Research · doi:10.1007/s12274-024-6776-1 · Cited by 10 · see citing works
The Essential Role of Astrocytes in Neurodegeneration and Neuroprotection
Couselo, F. L., Saba, J., Carniglia, L., Durand, D., Lasaga, M., & Caruso, C. M. (2023) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273269881231012062255 · Cited by 6 · see citing works
Pawar, S., Pingale, P., Garkal, A., Osmani, R. A. M., Gajbhiye, K. R., Kulkarni, M., Pardeshi, K., Mehta, T. A., & Rajput, A. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.131139 · Cited by 6 · see citing works
Concepts toward directing human astroplasticity to promote neuroregeneration
Patel, R., Muir, M. T., Cvetkovic, C., & Krencik, R. (2018) · Developmental Dynamics · doi:10.1002/dvdy.24655 · Cited by 5 · see citing works
Yang, Z., Jiang, X., & Gao, J. (2024) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2024.125069 · Cited by 5 · see citing works
Astrocytes phenomics as new druggable targets in healthy aging and Alzheimer’s disease progression
Lana, D., Ugolini, F., Iovino, L., Attorre, S., & Giovannini, M. G. (2025) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1512985 · Cited by 5 · see citing works
HIV Tat as a latency reversing agent: turning the tables on viral persistence
Fisher, B. M., Cevaal, P. M., Roche, M., & Lewin, S. R. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1571151 · Cited by 5 · see citing works
Advances in RNA delivery to extrahepatic tissues and cells
Li, Z., Guo, S., & Huang, Y. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.115170 · Cited by 4 · see citing works
Drug delivery systems for neural tissue engineering
Güler, E., Polat, E. B., & Çam, M. E. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-90554-1.00012-4 · Cited by 4 · see citing works
Delivery strategies of messenger RNA therapeutics for brain disorders
Youn, K., Oh, S., Gil, H.-W., Choi, Y., Keum, G., & Bang, E. (2025) · Bulletin of the Korean Chemical Society · doi:10.1002/bkcs.70083 · Cited by 3 · see citing works
Neuroglia targeting nano-therapeutic approaches to rescue aging and neurodegenerating brain
Sharma, M., Aggarwal, N., Mishra, J., & Panda, J. J. (2024) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2024.123950 · Cited by 2 · see citing works
Freire, J., Pang, S., McGee, J. E., Heinrich, M. J., Xie, J., Hammarlund, E., Shaw, D. C., Zhou, Y., Wang, Y., Porter, C., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.30.685635 · Cited by 1 · see citing works
Development of mRNA delivery system based on environment-sensitive lipid-like material
Tanaka, H. (2019) · Drug Delivery System · doi:10.2745/dds.34.60
Self-citationMechanistic studies of nanoparticle-mediated mRNA delivery
Masmanidou, O. (2018) · Chalmers Publication Library (Chalmers University of Technology)
Akita, H. (2020) · Drug Delivery System · doi:10.2745/dds.35.417
Self-citationDelivery systems and therapeutic applications of mRNA targeting the central nervous system
Uchida, S. (2023) · Drug Delivery System · doi:10.2745/dds.38.125
Nanoparticles in Delivery Across the Blood-Brain Barrier
Liu, J. (2025) · Theoretical and Natural Science · doi:10.54254/2753-8818/2025.au25804
Advanced lipid nanoparticles for targeted nucleic acid delivery
Deng, Y., Chen, M., Zhou, X., Luo, T., Guo, J., Giles, A., Mourin, T. T., & Chen, G. (2026) · Nano Research · doi:10.26599/nr.2026.94908809
Design and development of lipid nanoparticle formulations for brain gene therapy
Thomson, S. B., Gomes, A. D. M., Kazemian, P., Kurek, D. Z., Kulkarni, J. A., Saadati, F., Wagner, P. K., Petkau, T. L., Ciufolini, M. A., Cullis, P. R., et al. (2026) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2026.103025
Design, Preparation, and Optimization of mRNA Nanoemulsions for CNS Delivery
Lapuhs, P., Rubio-Prego, I., Pineiro‐Alonso, L., & Alonso, M. J. (2026) · Neuromethods · doi:10.1007/978-1-0716-5241-1_12
Emerging Lipid Nanoparticle Targeting Strategies for Extrahepatic Delivery of RNA Therapeutics
Li, J., Liu, J., Wang, N., Zhang, K., Zhang, W., Gao, M., Lu, Z., Chen, X. S., & Li, Y. (2026) · Advanced Materials · doi:10.1002/adma.75408
- Authors
- Tanaka, H., Nakatani, T., Furihata, T., Tange, K., Nakai, Y., Yoshioka, H., Harashima, H., & Akita, H.
- Affiliations
- Chiba University (JP)
- Hokkaido University (JP)
- NOF Corporation (Japan) (JP)
- Corresponding author
- Akita, Hidetaka
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-04-11
- Volume
- 15
- Issue
- 5
- Pages
- 2060-2067
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- OpenAlex
- W2797061403
- Cited by
- 82
- References
- 43
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 11 · 2023: 14 · 2022: 14 · 2021: 7 · 2020: 10 · 2019: 8 · 2018: 3
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Core Research for Evolutional Science and Technology (JPMJCR17H1)
- Asahi Glass Foundation
- Japan Society for the Promotion of Science (15H01806)
- 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 › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- lipid nanoparticles, mRNA delivery, intracerebroventricular administration, neurons, astrocytes, nerve growth factor, transfection
- MeSH terms
- Animals, Apolipoproteins E, Astrocytes, Brain, DNA, Lipids, Male, Mice, Inbred ICR, RNA, Messenger, Transfection, Mice, Nanoparticles, Infusions, Intraventricular
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
