Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids
Abstract
An analogous series of cationic lipids (1,2-distearyloxy-N,N-dimethyl-3-aminopropane (DSDMA), 1,2-dioleyloxy-N,N-dimethyl-3-aminopropane (DODMA), 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA) and 1,2-dilinolenyloxy-N,N-dimethyl-3-aminopropane (DLenDMA)) possessing 0, 1, 2 or 3 double bonds per alkyl chain respectively, was synthesized to determine the correlation between lipid saturation, fusogenicity and efficiency of intracellular nucleic acid delivery. 31P-NMR analysis suggests that as saturation increases, from 2 to 0 double bonds, lamellar (L(alpha)) to reversed hexagonal (H(II)) phase transition temperature increases, indicating decreasing fusogenicity. This trend is largely reflected by the efficiency of gene silencing observed in vitro when the lipids are formulated as Stable Nucleic Acid Lipid Particles (SNALPs) encapsulating small inhibitory RNA (siRNA). Uptake experiments suggest that despite their lower gene silencing efficiency, the less fusogenic particles are more readily internalized by cells. Microscopic visualization of fluorescently labelled siRNA uptake was supported by quantitative data acquired using radiolabelled preparations. Since electrostatic binding is a precursor to uptake, the pKa of each cationic lipid was determined. The results support a transfection model in which endosomal release, mediated by fusion with the endosomal membrane, results in cytoplasmic translocation of the nucleic acid payload.
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The ionizable cationic lipid DLinDMA is highly effective at delivering siRNA systemically in rodents and nonhuman primates.
“The ionizable cationic lipid 1,2-dilinoleyloxy-3-dimethylaminopropane (DLinDMA) (27), which is highly effective at delivering siRNA systemically in rodents and nonhuman primates, was used as the main component of the lipid nanoparticles.”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [27]
The delivery efficacy of mRNA could be improved by rational design of lipids through modulation of head groups and hydrophobic tails to increase cellular uptake and endosomal escape of lipid nanoparticle-mRNA formulations.
“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 [64]
Cites
Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure.
Felgner, P. L., Gadek, T. R., Holm, M., Roman, R., Chan, H. W., Wenz, M., Northrop, J. P., RINGOLD, G. M., & Danielsen, M. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.21.7413 · Cited by 4,954 · see citing works
Cellular and Molecular Barriers to Gene Transfer by a Cationic Lipid
Zabner, J., Fasbender, A., Moninger, T., Poellinger, K. A., & Welsh, M. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.32.18997 · Cited by 1,408 · see citing works
An Inverted Hexagonal Phase of Cationic Liposome-DNA Complexes Related to DNA Release and Delivery
Koltover, I., Salditt, T., Rädler, J. O., & Safinya, C. R. (1998) · Science · doi:10.1126/science.281.5373.78 · Cited by 1,336 · see citing works
Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations.
Felgner, J. H., Kumar, R., Sridhar, C. N., Wheeler, C. J., Tsai, Y.-L., Border, R., Ramsey, P., Martin, M. U., & Felgner, P. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41980-6 · Cited by 1,313 · see citing works
Mechanism of DNA Release from Cationic Liposome/DNA Complexes Used in Cell Transfection,
Xu, Y., & Szoka, F. C. (1996) · Biochemistry · doi:10.1021/bi9602019 · Cited by 1,136 · see citing works
The role of dioleoyl phosphatidylethanolamine in cationic liposome mediated gene transfer
Farhood, H., Serbina, N. V., & Huang, L. (1995) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(95)80016-9 · Cited by 799 · see citing works
On the mechanism whereby cationic lipids promote intracellular delivery of polynucleic acids
Hafez, I., Maurer, N., & Cullis, P. R. (2001) · Gene Therapy · doi:10.1038/sj.gt.3301506 · Cited by 601 · see citing works
Zhou, X., & Huang, L. (1994) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(94)90066-3 · Cited by 499 · see citing works
Phosphatodylethanolamine liposomes: drug delivery, gene transfer and immunodiagnostic applications
Litzinger, D. C., & Huang, L. (1992) · Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · doi:10.1016/0304-4157(92)90039-d · Cited by 368 · see citing works
Legendre, J., & Szoka, F. C. (1992) · Pharmaceutical Research · doi:10.1023/a:1015836829670 · Cited by 332 · see citing works
A Scalable, Extrusion-Free Method for Efficient Liposomal Encapsulation of Plasmid DNA
Jeffs, L. B., Palmer, L. R., Ambegia, E. G., Giesbrecht, C., Ewanick, S., & MacLachlan, I. (2005) · Pharmaceutical Research · doi:10.1007/s11095-004-1873-z · Cited by 307 · see citing works
Self-citationStabilized plasmid-lipid particles: construction and characterization
Wheeler, J. J., Palmer, L., Ossanlou, M., MacLachlan, I., Graham, R. W., Zhang, Y. P., Hope, M. J., Scherrer, P., & Cullis, P. R. (1999) · Gene Therapy · doi:10.1038/sj.gt.3300821 · Cited by 300 · see citing works
Self-citationLiu, F., Qi, H., Huang, L., & Liu, D. (1997) · Gene Therapy · doi:10.1038/sj.gt.3300424 · Cited by 247 · see citing works
Effect of cationic cholesterol derivatives on gene transfer and protein kinase C activity
Farhood, H., Bottega, R., Epand, R. M., & Huang, L. (1992) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(92)90316-e · Cited by 240 · see citing works
Ambegia, E., Ansell, S. M., Cullis, P. R., Heyes, J. A., Palmer, L., & MacLachlan, I. (2005) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2005.02.001 · Cited by 203 · see citing works
Self-citationSzule, J. A., Fuller, N. L., & Rand, R. P. (2002) · Biophysical Journal · doi:10.1016/s0006-3495(02)75223-5 · Cited by 196 · see citing works
Heyes, J. A., Niculescu‐Duvaz, D., Cooper, R. G., & Springer, C. J. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm010918g · Cited by 156 · see citing works
Self-citationStabilized plasmid-lipid particles for systemic gene therapy
Tam, P., Monck, M. A., Lee, D., Ludkovski, O., Leng, E. C., Clow, K. A., Stark, H., Scherrer, P., Graham, R. W., & Cullis, P. R. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301308 · Cited by 150 · see citing works
Modulation of Membrane Fusion by Asymmetric Transbilayer Distributions of Amino Lipids
Bailey, A. L., & Cullis, P. R. (1994) · Biochemistry · doi:10.1021/bi00208a007 · Cited by 143 · see citing works
Low-pH-Sensitive PEG-Stabilized Plasmid−Lipid Nanoparticles: Preparation and Characterization
Choi, J. S., MacKay, J. A., & Szoka, F. C. (2003) · Bioconjugate Chemistry · doi:10.1021/bc025625w · Cited by 109 · see citing works
Zhang, Y. P., Sekirov, L., Saravolac, E. G., Wheeler, J. J., Tardi, P. G., Clow, K. A., Leng, E. C., Sun, R. R., Cullis, P. R., & Scherrer, P. (1999) · Gene Therapy · doi:10.1038/sj.gt.3300965 · Cited by 108 · see citing works
Dekker, C. J., van Kessel, W. S. M. G., Klomp, J. P. G., Pieters, J., & KRUIJFF, B. D. (1983) · Chemistry and Physics of Lipids · doi:10.1016/0009-3084(83)90012-9 · Cited by 101 · see citing works
Mok, K. W. C., Lam, A. M. I., & Cullis, P. R. (1999) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(99)00059-0 · Cited by 96 · see citing works
Epand, R. M., Epand, R. F., Ahmed, N., & Chen, R. (1991) · Chemistry and Physics of Lipids · doi:10.1016/0009-3084(91)90051-c · Cited by 81 · see citing works
Epand, R. M., Fuller, N., & Rand, R. P. (1996) · Biophysical Journal · doi:10.1016/s0006-3495(96)79381-5 · Cited by 70 · see citing works
Sankaram, M. B., Powell, G. L., & Marsh, D. (1989) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(89)90331-3 · Cited by 64 · see citing works
Synthesis and Properties of Novel Tetraalkyl Cationic Lipids
Gaucheron, J., Wong, T., Wong, K. F., Maurer, N., & Cullis, P. R. (2002) · Bioconjugate Chemistry · doi:10.1021/bc0101259 · Cited by 52 · see citing works
Progress towards a synthetic virus for systemic gene therapy.
MacLachlan, I., Cullis, P. R., & Graham, R. W. (1999) · PubMed · Cited by 32 · see citing works
Self-citationWang, G., Li, S., Lin, H., Brumbaugh, E. E., & Huang, C.-H. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.18.12289 · Cited by 26 · see citing works
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Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076 · see citing works
Non-viral vectors for gene-based therapy
Yin, H., Kanasty, R. L., Eltoukhy, A. A., Vegas, A. J., Dorkin, J. R., & Anderson, D. G. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3763 · Cited by 3,123 · 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
Self-citationmRNA vaccines for infectious diseases: principles, delivery and clinical translation
Chaudhary, N., Weissman, D., & Whitehead, K. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00283-5 · Cited by 1,555 · 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
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
The role of lipid components in lipid nanoparticles for vaccines and gene therapy
Gregersen, C. H., Kulkarni, J. A., Witzigmann, D., Lind, M. L., Petersson, K., & Simonsen, J. B. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114416 · Cited by 1,215 · see citing works
Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery
Kowalski, P. S., Rudra, A., Miao, L., & Anderson, D. G. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.02.012 · Cited by 1,127 · see citing works
Lipid-like materials for low-dose, in vivo gene silencing
Love, K. T., Mahon, K. P., Levins, C. G., Whitehead, K. A., Querbes, W., Dorkin, J. R., Qin, J., Cantley, W., Qin, L. L., Racie, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910603106 · Cited by 969 · see citing works
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
Therapeutic siRNA silencing in inflammatory monocytes in mice
Leuschner, F., Dutta, P., Gorbatov, R., Novobrantseva, T. I., Donahoe, J. S., Courties, G., Lee, K. M., Kim, J. I., Markmann, J. F., Marinelli, B., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1989 · Cited by 839 · see citing works
Sabnis, S., Kumarasinghe, E. S., Salerno, T., Mihai, C., Ketova, T., Senn, J. J., Lynn, A., Bulychev, A., McFadyen, I., Chan, J., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.03.010 · Cited by 820 · 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
Miao, L., Li, L., Huang, Y., Delcassian, D., Chahal, J., Han, J., Shi, Y., Sadtler, K., Gao, W., Lin, J., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0247-3 · Cited by 723 · see citing works
Lipid Nanoparticle Assisted mRNA Delivery for Potent Cancer Immunotherapy
Oberli, M. A., Reichmuth, A. M., Dorkin, J. R., Mitchell, M. J., Fenton, O. S., Jaklenec, A., Anderson, D. G., Langer, R., & Blankschtein, D. (2017) · Nano Letters · doi:10.1021/acs.nanolett.6b03329 · Cited by 719 · see citing works
Nonviral delivery of self-amplifying RNA vaccines
Geall, A. J., Verma, A., Otten, G. R., Shaw, C. A., Hekele, A., Banerjee, K., Cu, Y., Beard, C. W., Brito, L. A., Krucker, T., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209367109 · Cited by 675 · see citing works
Kulkarni, J. A., Darjuan, M. M., Mercer, J. E., Chen, S., van der Meel, R., Thewalt, J. L., Tam, Y. Y. C., & Cullis, P. R. (2018) · ACS Nano · doi:10.1021/acsnano.8b01516 · Cited by 663 · see citing works
Breaking down the barriers: siRNA delivery and endosome escape
Domińska, M., & Dykxhoorn, D. M. (2010) · Journal of Cell Science · doi:10.1242/jcs.066399 · Cited by 632 · 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
An ionizable lipid toolbox for RNA delivery
Han, X., Zhang, H., Butowska, K., Swingle, K. L., Alameh, M.-G., Weissman, D., & Mitchell, M. J. (2021) · Nature Communications · doi:10.1038/s41467-021-27493-0 · Cited by 628 · see citing works
Ionizable Lipid Nanoparticle-Mediated mRNA Delivery for Human CAR T Cell Engineering
Billingsley, M. M., Singh, N., Ravikumar, P., Zhang, R., June, C. H., & Mitchell, M. J. (2020) · Nano Letters · doi:10.1021/acs.nanolett.9b04246 · Cited by 636 · 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
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
Self-citationNanomaterial Delivery Systems for mRNA Vaccines
Buschmann, M. D., Carrasco, M. J., Alishetty, S., Paige, M., Alameh, M. G., & Weissman, D. (2021) · Vaccines · doi:10.3390/vaccines9010065 · Cited by 582 · see citing works
Strategies, design, and chemistry in siRNA delivery systems
Dong, Y., Siegwart, D. J., & Anderson, D. G. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.05.004 · Cited by 581 · see citing works
Design of Noninflammatory Synthetic siRNA Mediating Potent Gene Silencing in Vivo
Judge, A. D., Bola, G., Lee, A. C. H., & MacLachlan, I. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.11.002 · Cited by 571 · see citing works
Self-citationLipid Nanoparticle Technology for Clinical Translation of siRNA Therapeutics
Kulkarni, J. A., Witzigmann, D., Chen, S., Cullis, P. R., & van der Meel, R. (2019) · Accounts of Chemical Research · doi:10.1021/acs.accounts.9b00368 · Cited by 534 · see citing works
mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases
Maruggi, G., Zhang, C., Li, J., Ulmer, J. B., & Yu, D. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.01.020 · Cited by 507 · see citing works
The 60-year evolution of lipid nanoparticles for nucleic acid delivery
Cullis, P. R., & Felgner, P. L. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-00977-6 · Cited by 517 · see citing works
Kim, J., Eygeris, Y., Gupta, M., & Sahay, G. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.12.014 · Cited by 514 · see citing works
Geisbert, T. W., Lee, A. C., Robbins, M., Geisbert, J. B., Honko, A. N., Sood, V., Johnson, J. C., de Jong, S. D., Tavakoli, I., Judge, A. D., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60357-1 · Cited by 457 · see citing works
Self-citationA Comprehensive Review of mRNA Vaccines
Gote, V., Bolla, P. K., Kommineni, N., Butreddy, A., Nukala, P. K., Palakurthi, S. S., & Khan, W. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032700 · Cited by 457 · see citing works
Carrasco, M. J., Alishetty, S., Alameh, M., Said, H., Wright, L., Paige, M. A., Soliman, O. Y., Weissman, D., Cleveland, T. E., Grishaev, A., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02441-2 · Cited by 445 · see citing works
Chemically modified siRNA: tools and applications
Watts, J. K., Deleavey, G. F., & Damha, M. J. (2008) · Drug Discovery Today · doi:10.1016/j.drudis.2008.05.007 · Cited by 431 · see citing works
Chen, D. L., Love, K. T., Chen, Y., Eltoukhy, A. A., Kastrup, C. J., Sahay, G., Jeon, A., Dong, Y., Whitehead, K. A., & Anderson, D. G. (2012) · Journal of the American Chemical Society · doi:10.1021/ja301621z · Cited by 422 · 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
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
Kim, M., Jeong, M., Hur, S., Cho, Y., Park, J., Jung, H. R., Seo, Y., Woo, H., Nam, K. T., Lee, K., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf4398 · Cited by 390 · see citing works
Cytosolic delivery of nucleic acids: The case of ionizable lipid nanoparticles
Schlich, M., Palomba, R., Costabile, G., Mizrahy, S., Pannuzzo, M., Peer, D., & Decuzzi, P. (2021) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10213 · Cited by 387 · 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
Lipid nanoparticle technology for therapeutic gene regulation in the liver
Witzigmann, D., Kulkarni, J. A., Leung, J., Chen, S., Cullis, P. R., & van der Meel, R. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.06.026 · Cited by 376 · see citing works
Recent advances in siRNA delivery mediated by lipid-based nanoparticles
Yonezawa, S., Koide, H., & Asai, T. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.07.022 · Cited by 386 · see citing works
Targeting the transferrin receptor for brain drug delivery
Johnsen, K. B., Burkhart, A., Thomsen, L. B., Andresen, T. L., & Moos, T. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101665 · Cited by 371 · see citing works
Polymeric Delivery of Therapeutic Nucleic Acids
Kumar, R., Chalarca, C. F. S., Bockman, M. R., Bruggen, C. V., Grimme, C. J., Dalal, R. J., Hanson, M. G., Hexum, J. K., & Reineke, T. M. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00997 · Cited by 370 · see citing works
Development of Lipidoid–siRNA Formulations for Systemic Delivery to the Liver
Akinc, A., Goldberg, M. S., Qin, J., Dorkin, J. R., Gamba‐Vitalo, C., Maier, M. A., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Manoharan, M., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2009.36 · Cited by 353 · see citing works
Concise Review: Developing Best-Practice Models for the Therapeutic Use of Extracellular Vesicles
Reiner, A. T., Witwer, K. W., van Balkom, B. W. M., de Beer, J., Brodie, C., Corteling, R. L., Gabrielsson, S., Gimona, M., Ibrahim, A., de Kleijn, D. P. V., et al. (2017) · Stem Cells Translational Medicine · doi:10.1002/sctm.17-0055 · Cited by 351 · see citing works
Synergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver
Miao, L., Lin, J., Huang, Y., Li, L., Delcassian, D., Ge, Y., Shi, Y., & Anderson, D. G. (2020) · Nature Communications · doi:10.1038/s41467-020-16248-y · Cited by 343 · see citing works
High-Density Lipoproteins: Nature’s Multifunctional Nanoparticles
Kuai, R., Li, D., Chen, Y. E., Moon, J. J., & Schwendeman, A. A. (2016) · ACS Nano · doi:10.1021/acsnano.5b07522 · Cited by 341 · see citing works
Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics
Dahlman, J. E., Kauffman, K. J., Xing, Y., Shaw, T. E., Mir, F. F., Dlott, C. C., Langer, R., Anderson, D. G., & Wang, E. T. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620874114 · Cited by 335 · see citing works
Nucleic acid delivery for therapeutic applications
Gupta, A., Andresen, J. L., Manan, R. S., & Langer, R. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113834 · Cited by 339 · see citing works
Evers, M. J. W., Kulkarni, J. A., van der Meel, R., Cullis, P. R., Vader, P., & Schiffelers, R. M. (2018) · Small Methods · doi:10.1002/smtd.201700375 · Cited by 332 · see citing works
Scalable mRNA and siRNA Lipid Nanoparticle Production Using a Parallelized Microfluidic Device
Shepherd, S. J., Warzecha, C. C., Yadavali, S., El-Mayta, R. D., Alameh, M., Wang, L., Weissman, D., Wilson, J. M., Issadore, D., & Mitchell, M. J. (2021) · Nano Letters · doi:10.1021/acs.nanolett.1c01353 · Cited by 319 · see citing works
Lipid-Based DNA Therapeutics: Hallmarks of Non-Viral Gene Delivery
Buck, J., Grossen, P., Cullis, P. R., Huwyler, J., & Witzigmann, D. (2019) · ACS Nano · doi:10.1021/acsnano.8b07858 · Cited by 318 · see citing works
Hajj, K. A., Ball, R. L., Deluty, S. B., Singh, S. R., Strelkova, D., Knapp, C. M., & Whitehead, K. A. (2019) · Small · doi:10.1002/smll.201805097 · Cited by 312 · 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
Efficient and targeted delivery of siRNA in vivo
Shim, M. S., & Kwon, Y. J. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07904.x · Cited by 311 · see citing works
Fenton, O. S., Kauffman, K. J., Kaczmarek, J. C., McClellan, R. L., Jhunjhunwala, S., Tibbitt, M. W., Zeng, M. D., Appel, E. A., Dorkin, J. R., Mir, F. F., et al. (2017) · Advanced Materials · doi:10.1002/adma.201606944 · Cited by 289 · see citing works
The Importance of Apparent pKa in the Development of Nanoparticles Encapsulating siRNA and mRNA
Patel, P., Ibrahim, N. M., & Cheng, K. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2021.03.002 · Cited by 293 · see citing works
A novel mechanism for the loss of mRNA activity in lipid nanoparticle delivery systems
Packer, M., Gyawali, D., Yerabolu, R., Schariter, J., & White, P. (2021) · Nature Communications · doi:10.1038/s41467-021-26926-0 · Cited by 279 · see citing works
Advances in gene delivery through molecular design of cationic lipids
Bhattacharya, S., & Bajaj, A. (2009) · Chemical Communications · doi:10.1039/b900666b · Cited by 265 · see citing works
From influenza to COVID-19: Lipid nanoparticle mRNA vaccines at the frontiers of infectious diseases
Pilkington, E. H., Suys, E. J. A., Trevaskis, N. L., Wheatley, A. K., Zukancic, D., Algarni, A., Al-Wassiti, H. A., Davis, T. P., Pouton, C. W., Kent, S. J., et al. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.06.023 · Cited by 265 · 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
Fenske, D. B., & Cullis, P. R. (2007) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.5.1.25 · Cited by 256 · see citing works
Lipid-Based Nanoparticles for siRNA Delivery in Cancer Therapy: Paradigms and Challenges
Gomes-da-Silva, L. C., Fonseca, N. A., Moura, V., de Lima, M. C. P., Simões, S., & Moreira, J. N. (2012) · Accounts of Chemical Research · doi:10.1021/ar300048p · Cited by 254 · see citing works
Geisbert, T. W., Hensley, L. E., Kagan, E., Yu, E. Z., Geisbert, J. B., Daddario-DiCaprio, K. M., Fritz, E. A., Jahrling, P. B., McClintock, K., Phelps, J. R., et al. (2006) · The Journal of Infectious Diseases · doi:10.1086/504267 · Cited by 254 · see citing works
Self-citationBioinspired Alkenyl Amino Alcohol Ionizable Lipid Materials for Highly Potent In Vivo mRNA Delivery
Fenton, O. S., Kauffman, K. J., McClellan, R. L., Appel, E. A., Dorkin, J. R., Tibbitt, M. W., Heartlein, M. W., DeRosa, F., Langer, R., & Anderson, D. G. (2016) · Advanced Materials · doi:10.1002/adma.201505822 · Cited by 254 · see citing works
Structure and Function of Cationic and Ionizable Lipids for Nucleic Acid Delivery
Sun, D., & Lu, Z. (2023) · Pharmaceutical Research · doi:10.1007/s11095-022-03460-2 · Cited by 253 · see citing works
Lipid Nanoparticles as Delivery Systems for RNA-Based Vaccines
Aldosari, B. N., Alfagih, I. M., & Almurshedi, A. S. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13020206 · Cited by 242 · see citing works
An RNA toolbox for cancer immunotherapy
Pastor, F., Berraondo, P., Etxeberria, I., Frederick, J., Sahin, U., Gilboa, E., & Melero, I. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.132 · Cited by 229 · see citing works
Design of lipid nanoparticles for in vitro and in vivo delivery of plasmid DNA
Kulkarni, J. A., Myhre, J. L., Chen, S., Tam, Y. Y. C., Danescu, A., Richman, J. M., & Cullis, P. R. (2016) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2016.12.014 · Cited by 229 · see citing works
Advances in lipid nanoparticles for siRNA delivery
Tam, Y., Chen, S., & Cullis, P. (2013) · Pharmaceutics · doi:10.3390/pharmaceutics5030498 · Cited by 229 · see citing works
Rapidly produced SAM <sup>®</sup> vaccine against H7N9 influenza is immunogenic in mice
Hekele, A., Bertholet, S., Archer, J., Gibson, D. G., Palladino, G., Brito, L. A., Otten, G. R., Brazzoli, M., Buccato, S., Bonci, A., et al. (2013) · Emerging Microbes & Infections · doi:10.1038/emi.2013.54 · Cited by 226 · see citing works
Kheirolomoom, A., Dayton, P. A., Lum, A. F. H., Little, E. L., Paoli, E. E., Zheng, H., & Ferrara, K. W. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.12.015 · Cited by 225 · see citing works
Kumar, V., Qin, J., Jiang, Y., Duncan, R. G., Brigham, B., Fishman, S., Nair, J. K., Akinc, A., Barros, S. A., & Kasperkovitz, P. V. (2014) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2014.61 · Cited by 222 · see citing works
Ionizable lipid nanoparticles for in utero mRNA delivery
Riley, R. S., Kashyap, M. V., Billingsley, M. M., White, B., Alameh, M.-G., Bose, S. K., Zoltick, P. W., Li, H., Zhang, R., Cheng, A. Y., et al. (2021) · Science Advances · doi:10.1126/sciadv.aba1028 · Cited by 222 · see citing works
Hatakeyama, H., Akita, H., Ito, E., Hayashi, Y., Oishi, M., Nagasaki, Y., Danev, R., Nagayama, K., Kaji, N., Kikuchi, H., et al. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.02.045 · Cited by 218 · see citing works
Nanoparticles Escaping RES and Endosome: Challenges for siRNA Delivery for Cancer Therapy
Guo, S., & Huang, L. (2011) · Journal of Nanomaterials · doi:10.1155/2011/742895 · Cited by 217 · see citing works
Formulation and Delivery Technologies for mRNA Vaccines
Zeng, C., Zhang, C., Walker, P. G., & Dong, Y. (2020) · Current topics in microbiology and immunology · doi:10.1007/82_2020_217 · Cited by 221 · see citing works
A Combinatorial Library of Lipid Nanoparticles for RNA Delivery to Leukocytes
Ramishetti, S., Hazan‐Halevy, I., Palakuri, R., Chatterjee, S., Naidu, G. S., Dammes, N., Freilich, I., Shmuel, L. K., Danino, D., & Peer, D. (2020) · Advanced Materials · doi:10.1002/adma.201906128 · Cited by 212 · see citing works
Pepini, T., Pulichino, A.-M., Carsillo, T., Carlson, A. L., Sari-Sarraf, F., Ramsauer, K., Debasitis, J. C., Maruggi, G., Otten, G. R., Geall, A. J., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601877 · Cited by 208 · see citing works
Artificial intelligence-driven rational design of ionizable lipids for mRNA delivery
Wang, W., Chen, K., Jiang, T. S., Wu, Y., Wu, Z., Ying, H., Yu, H., Lu, J., Lin, J., & Ouyang, D. (2024) · Nature Communications · doi:10.1038/s41467-024-55072-6 · Cited by 220 · see citing works
Octaarginine-modified multifunctional envelope-type nano device for siRNA
Nakamura, Y., Kogure, K., Futaki, S., & Harashima, H. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.03.010 · Cited by 201 · see citing works
Next-Generation Lipids in RNA Interference Therapeutics
Rietwyk, S., & Peer, D. (2017) · ACS Nano · doi:10.1021/acsnano.7b04734 · Cited by 199 · see citing works
Lipid nanoparticle delivery systems for siRNA-based therapeutics
Wan, C. P. L., Allen, T. M., & Cullis, P. R. (2013) · Drug Delivery and Translational Research · doi:10.1007/s13346-013-0161-z · Cited by 194 · see citing works
Kauffman, K. J., Mir, F. F., Jhunjhunwala, S., Kaczmarek, J. C., Hurtado, J. E., Yang, J. H., Webber, M. J., Kowalski, P. S., Heartlein, M. W., DeRosa, F., et al. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.09.006 · Cited by 191 · see citing works
Combinatorial development of nebulized mRNA delivery formulations for the lungs
Jiang, A. Y., Witten, J. J., Raji, I. O., Eweje, F., MacIsaac, C., Meng, S., Oladimeji, F. A., Hu, Y., Manan, R. S., Langer, R., et al. (2023) · Nature Nanotechnology · doi:10.1038/s41565-023-01548-3 · Cited by 191 · see citing works
Multiparametric approach for the evaluation of lipid nanoparticles for siRNA delivery
Alabi, C. A., Love, K. T., Sahay, G., Yin, H., Luly, K. M., Langer, R., & Anderson, D. G. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1306529110 · Cited by 188 · see citing works
How cationic lipids transfer nucleic acids into cells and across cellular membranes: Recent advances
Rehman, Z. U., Zuhorn, I. S., & Hoekstra, D. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.12.014 · Cited by 186 · see citing works
Bost, J., Barriga, H. M. G., Holme, M. N., Gallud, A., Maugeri, M., Gupta, D., Lehto, T., Valadi, H., Esbjörner, E. K., Stevens, M. M., et al. (2021) · ACS Nano · doi:10.1021/acsnano.1c05099 · Cited by 187 · see citing works
RNA: The new revolution in nucleic acid vaccines
Geall, A. J., Mandl, C. W., & Ulmer, J. B. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.05.001 · Cited by 187 · see citing works
Recent Advances in the Lipid Nanoparticle-Mediated Delivery of mRNA Vaccines
Swetha, K., Kotla, N. G., Tunki, L., Jayaraj, A., Bhargava, S. K., Hu, H., Bonam, S. R., & Kurapati, R. (2023) · Vaccines · doi:10.3390/vaccines11030658 · Cited by 190 · see citing works
Nucleic acid drugs: recent progress and future perspectives
Sun, X., Setrerrahmane, S., Li, C., Hu, J., & Xu, H. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02035-4 · Cited by 202 · see citing works
Brito, L. A., Kommareddy, S., Maione, D., Uematsu, Y., Giovani, C., Scorza, F. B., Otten, G. R., Yu, D. L., Mandl, C. W., Mason, P. W., et al. (2014) · Advances in genetics · doi:10.1016/bs.adgen.2014.10.005 · Cited by 182 · see citing works
Lipid Nanoparticles for Gene Delivery
Zhao, Y. D., & Huang, L. (2014) · Advances in genetics · doi:10.1016/b978-0-12-800148-6.00002-x · Cited by 182 · see citing works
Billingsley, M. M., Hamilton, A. G., Mai, D., Patel, S. K., Swingle, K. L., Sheppard, N. C., June, C. H., & Mitchell, M. J. (2021) · Nano Letters · doi:10.1021/acs.nanolett.1c02503 · Cited by 180 · 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
Cationic lipid nanoparticles for therapeutic delivery of siRNA and miRNA to murine liver tumor
Hsu, S., Yu, B., Wang, X., Lu, Y., Schmidt, C. R., Lee, R. J., Lee, L. J., Jacob, S. T., & Ghoshal, K. (2013) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2013.05.007 · Cited by 174 · see citing works
RNAi-based nanomedicines for targeted personalized therapy
Daka, A., & Peer, D. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.08.014 · Cited by 168 · see citing works
Li, B., Jiang, A. Y., Raji, I. O., Atyeo, C. G., Raimondo, T. M., Gordon, A. G. R., Rhym, L. H., Samad, T. S., MacIsaac, C., Witten, J. J., et al. (2023) · Nature Biomedical Engineering · doi:10.1038/s41551-023-01082-6 · Cited by 167 · see citing works
- Authors
- Heyes, J., Palmer, L., Bremner, K., & MacLachlan, I.
- Corresponding author
- MacLachlan, Ian
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 107
- Issue
- 2
- Pages
- 276-287
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2086919915
- Cited by
- 572
- References
- 29
- Citations by year
- 2026: 27 · 2025: 52 · 2024: 65 · 2023: 51 · 2022: 41 · 2021: 49 · 2020: 23 · 2019: 30 · 2018: 17 · 2017: 29 · 2016: 23 · 2015: 15 · 2014: 23 · 2013: 24 · 2012: 29
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of British Columbia
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- cationic lipids, lipid saturation, siRNA, gene silencing, fusogenicity, lipid phase transition, endosomal escape, endosomal membrane fusion, electrostatic binding, pKa, lipogenesis
- MeSH terms
- Cations, Cell Line, Chemistry, Pharmaceutical, Drug Compounding, Humans, Lipids, Luciferases, Neurons, Magnetic Resonance Spectroscopy, Toluene, Transfection, Gene Expression, Drug Delivery Systems, Gene Silencing, RNA, Small Interfering
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