RNAi-mediated gene silencing in non-human primates
Abstract
The opportunity to harness the RNA interference (RNAi) pathway to silence disease-causing genes holds great promise for the development of therapeutics directed against targets that are otherwise not addressable with current medicines. Although there are numerous examples of in vivo silencing of target genes after local delivery of small interfering RNAs (siRNAs), there remain only a few reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and there are no reports of systemic efficacy in non-rodent species. Here we show that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B (ApoB) in non-human primates. APOB-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP) and administered by intravenous injection to cynomolgus monkeys at doses of 1 or 2.5 mg kg(-1). A single siRNA injection resulted in dose-dependent silencing of APOB messenger RNA expression in the liver 48 h after administration, with maximal silencing of >90%. This silencing effect occurred as a result of APOB mRNA cleavage at precisely the site predicted for the RNAi mechanism. Significant reductions in ApoB protein, serum cholesterol and low-density lipoprotein levels were observed as early as 24 h after treatment and lasted for 11 days at the highest siRNA dose, thus demonstrating an immediate, potent and lasting biological effect of siRNA treatment. Our findings show clinically relevant RNAi-mediated gene silencing in non-human primates, supporting RNAi therapeutics as a potential new class of drugs.
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Liposome-encapsulated siRNA has the potential to achieve systemic lipid-lowering.
“This study demonstrates the potential of systemic lipid-lowering by liposome-encapsulated siRNA.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [76]
siRNA therapy can be applied for treating GARDs by targeted silencing of the disease-causing genes.
“Therefore, siRNA therapy can be applied for treating GARDs by targeted silencing of the disease-causing genes.[50, 52]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [52]
Cites
A Receptor-Mediated Pathway for Cholesterol Homeostasis
Brown, M. S., & Goldstein, J. L. (1986) · Science · doi:10.1126/science.3513311 · Cited by 5,703 · see citing works
Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes
Cannon, C. P., Braunwald, E., McCabe, C. H., Rader, D. J., Rouleau, J. L., Belder, R., Joyal, S. V., Hill, K. A., Pfeffer, M. A., & Skene, A. M. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040583 · Cited by 4,938 · see citing works
C-Reactive Protein Levels and Outcomes after Statin Therapy
Ridker, P. M., Cannon, C. P., Morrow, D., Rifai, N., Rose, L. M., McCabe, C. H., Pfeffer, M. A., & Braunwald, E. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa042378 · Cited by 2,292 · 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
Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA
Judge, A. D., Sood, V., Shaw, J. R., Fang, D., McClintock, K., & MacLachlan, I. (2005) · Nature Biotechnology · doi:10.1038/nbt1081 · Cited by 1,250 · see citing works
Hornung, V., Guenthner‐Biller, M., Bourquin, C., Ablasser, A., Schlee, M., Uematsu, S., Noronha, A. M., Manoharan, M., Akira, S., de Fougerolles, A., et al. (2005) · Nature Medicine · doi:10.1038/nm1191 · Cited by 1,233 · see citing works
Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs
Morrissey, D. V., Lockridge, J. A., Shaw, L., Blanchard, K. S., Jensen, K., Breen, W., Hartsough, K. C., Machemer, L., Radka, S. F., Jadhav, V., et al. (2005) · Nature Biotechnology · doi:10.1038/nbt1122 · Cited by 1,168 · see citing works
Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors
Song, E., Zhu, P., Lee, S., Chowdhury, D., Kussman, S., Dykxhoorn, D. M., Feng, Y., Palliser, D., Weiner, D. B., Shankar, P., et al. (2005) · Nature Biotechnology · doi:10.1038/nbt1101 · Cited by 1,022 · see citing works
Novina, C. D., & Sharp, P. A. (2004) · Nature · doi:10.1038/430161a · Cited by 730 · see citing works
Inhibition of respiratory viruses by nasally administered siRNA
Bitko, V., Musiyenko, A., Shulyayeva, O., & Barik, S. (2004) · Nature Medicine · doi:10.1038/nm1164 · Cited by 725 · see citing works
Bartlett, D. W. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj439 · Cited by 593 · see citing works
Lennernäs, H., & Fager, G. (1997) · Clinical Pharmacokinetics · doi:10.2165/00003088-199732050-00005 · Cited by 527 · see citing works
Levin, A. A. (1999) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(99)00140-2 · Cited by 438 · see citing works
An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection
Palliser, D., Chowdhury, D., Wang, Q.-Y., Lee, S. J., Bronson, R. T., Knipe, D. M., & Lieberman, J. (2006) · Nature · doi:10.1038/nature04263 · Cited by 410 · see citing works
Chonn, A., Cullis, P. R., & Devine, D. V. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.12.4234 · Cited by 367 · see citing works
Diamond, G., Beckloff, N., Ryan, L. K., Res, J. D., Diamond, G., Beckloff, N., & Ryan, L. K. (2005) · SAGE Publications Ltd eBooks · doi:10.4135/9781849208765.n5 · Cited by 339 · see citing works
Song, E., Lee, S., Dykxhoorn, D. M., Novina, C. D., Zhang, D., Crawford, K. D., Černý, J., Sharp, P. A., Lieberman, J., Manjunath, N., et al. (2003) · Journal of Virology · doi:10.1128/jvi.77.13.7174-7181.2003 · Cited by 230 · see citing works
Crooke, R. M., Graham, M. J., Lemonidis, K. M., Whipple, C. P., Koo, S., & Perera, R. J. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m400492-jlr200 · Cited by 224 · see citing works
Thakker, D. R., Natt, F., Hüsken, D., Maier, R., Müller, M., van der Putten, H., Hoyer, D., & Cryan, J. F. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406214101 · Cited by 211 · see citing works
The Prospect of Silencing Disease Using RNA Interference
Shankar, P. (2005) · JAMA · doi:10.1001/jama.293.11.1367 · Cited by 140 · see citing works
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Liposomal drug delivery systems: From concept to clinical applications
Allen, T. M., & Cullis, P. R. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.037 · Cited by 4,839 · 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
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
Advances in oligonucleotide drug delivery
Roberts, T. C., Langer, R., & Wood, M. J. A. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0075-7 · Cited by 2,026 · 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
Delivery materials for siRNA therapeutics
Kanasty, R., Dorkin, J. R., Vegas, A., & Anderson, D. (2013) · Nature Materials · doi:10.1038/nmat3765 · Cited by 1,800 · see citing works
The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs
Akinc, A., Maier, M. A., Manoharan, M., Fitzgerald, K., Jayaraman, M., Barros, S., Ansell, S., Du, X., Hope, M. J., Madden, T. D., et al. (2019) · Nature Nanotechnology · doi:10.1038/s41565-019-0591-y · Cited by 1,636 · see citing works
Therapeutic siRNA: state of the art
Hu, B., Zhong, L., Weng, Y., Peng, L., Huang, Y., Zhao, Y., & Liang, X.-J. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0207-x · Cited by 1,586 · see citing works
Tabas, I., Williams, K. J., & Borén, J. (2007) · Circulation · doi:10.1161/circulationaha.106.676890 · Cited by 1,399 · see citing works
Bennett, C. F., & Swayze, E. E. (2010) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105654 · Cited by 1,381 · see citing works
The current landscape of nucleic acid therapeutics
Kulkarni, J. A., Witzigmann, D., Thomson, S. B., Chen, S., Leavitt, B. R., Cullis, P. R., & van der Meel, R. (2021) · Nature Nanotechnology · doi:10.1038/s41565-021-00898-0 · Cited by 1,371 · see citing works
Drug delivery systems for RNA therapeutics
Paunovska, K., Loughrey, D., & Dahlman, J. E. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00439-4 · Cited by 1,349 · 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
Nanomaterials for Theranostics: Recent Advances and Future Challenges
Lim, E., Kim, T., Paik, S., Haam, S., Huh, Y., & Lee, K. (2014) · Chemical Reviews · doi:10.1021/cr300213b · Cited by 1,236 · 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 promises and pitfalls of RNA-interference-based therapeutics
Castanotto, D., & Rossi, J. J. (2009) · Nature · doi:10.1038/nature07758 · Cited by 1,219 · see citing works
Interfering with disease: a progress report on siRNA-based therapeutics
de Fougerolles, A., Vornlocher, H., Maraganore, J. M., & Lieberman, J. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2310 · Cited by 1,202 · see citing works
Lipid Nanoparticle Systems for Enabling Gene Therapies
Cullis, P. R., & Hope, M. J. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.03.013 · Cited by 1,208 · see citing works
Overcoming cellular barriers for RNA therapeutics
Dowdy, S. F. (2017) · Nature Biotechnology · doi:10.1038/nbt.3802 · Cited by 1,139 · see citing works
Transvascular delivery of small interfering RNA to the central nervous system
Kumar, P., Wu, H., McBride, J. L., Jung, K.-E., Hee Kim, M., Davidson, B. L., Kyung Lee, S., Shankar, P., & Manjunath, N. (2007) · Nature · doi:10.1038/nature05901 · Cited by 1,246 · see citing works
Jackson, A. L., & Linsley, P. S. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd3010 · Cited by 1,092 · see citing works
RNAi therapeutics: a potential new class of pharmaceutical drugs
Bumcrot, D. A., Manoharan, M., Koteliansky, V., & Sah, D. W. Y. (2006) · Nature Chemical Biology · doi:10.1038/nchembio839 · Cited by 1,086 · see citing works
Strategies for silencing human disease using RNA interference
Kim, D. H., & Rossi, J. J. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2006 · Cited by 1,078 · see citing works
Illuminating the silence: understanding the structure and function of small RNAs
Rana, T. M. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2085 · Cited by 837 · see citing works
Therapeutic targeting of microRNAs: current status and future challenges
Li, Z., & Rana, T. M. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4359 · Cited by 1,028 · see citing works
The miR-15a–miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities
Bonci, D., Coppola, V., Musumeci, M., Addario, A., Giuffrida, R., Memeo, L., D’Urso, L., Pagliuca, A., Biffoni, M., Labbaye, C., et al. (2008) · Nature Medicine · doi:10.1038/nm.1880 · Cited by 989 · 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
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
RNAi therapeutics: Principles, prospects and challenges
Aagaard, L., & Rossi, J. J. (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.03.005 · Cited by 895 · see citing works
Functional Aptamers and Aptazymes in Biotechnology, Diagnostics, and Therapy
Famulok, M., Hartig, J. S., & Mayer, G. (2007) · Chemical Reviews · doi:10.1021/cr0306743 · Cited by 889 · see citing works
Chemistry, structure and function of approved oligonucleotide therapeutics
Egli, M., & Manoharan, M. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad067 · Cited by 864 · see citing works
Bartlett, D. W., Su, H. C., Hildebrandt, I. J., Weber, W., & Davis, M. E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707461104 · Cited by 808 · see citing works
Knocking down disease: a progress report on siRNA therapeutics
Wittrup, A., & Lieberman, J. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3978 · Cited by 810 · see citing works
Delivery of siRNA Therapeutics: Barriers and Carriers
Wang, J., Lu, Z., Wientjes, M. G., & Au, J. L. ‐. (2010) · The AAPS Journal · doi:10.1208/s12248-010-9210-4 · Cited by 804 · see citing works
Progress in developing cationic vectors for non-viral systemic gene therapy against cancer
Morille, M., Passirani, C., Vonarbourg, A., Clavreul, A., & Benoît, J. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.04.036 · Cited by 769 · see citing works
Current prospects for RNA interference-based therapies
Davidson, B. L., & McCray, P. B. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2968 · Cited by 760 · see citing works
Therapeutic miRNA and siRNA: Moving from Bench to Clinic as Next Generation Medicine
Chakraborty, C., Sharma, A. R., Sharma, G., Doss, C. G. P., & Lee, S. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2017.06.005 · Cited by 731 · see citing works
Mendes, B. B., Conniot, J., Avital, A., Yao, D., Jiang, X., Zhou, X., Sharf-Pauker, N., Xiao, Y., Adir, O., Liang, H., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00104-y · Cited by 719 · see citing works
GalNAc-siRNA conjugates: leading the way for delivery of RNAi therapeutics
Springer, A. D., & Dowdy, S. F. (2018) · Nucleic Acid Therapeutics · doi:10.1089/nat.2018.0736 · Cited by 711 · see citing works
Supramolecular self-assemblies as functional nanomaterials
Busseron, E., Ruff, Y., Moulin, É., & Giuseppone, N. (2013) · Nanoscale · doi:10.1039/c3nr02176a · Cited by 699 · see citing works
Tabernero, J. M., Shapiro, G. I., LoRusso, P. M., Cervantes, A. M. R., Schwartz, G. K., Weiss, G. J., Paz-Ares, L. G., Cho, D. C., Infante, J. R., Alsina, M., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0429 · Cited by 700 · see citing works
In vivo imaging of siRNA delivery and silencing in tumors
Medarova, Z., Pham, W., Farrar, C., Petkova, V., & Moore, A. (2007) · Nature Medicine · doi:10.1038/nm1486 · Cited by 697 · see citing works
The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery
Cheng, X., & Lee, R. J. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.01.022 · Cited by 703 · see citing works
Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown
Wittrup, A., Ai, A., Liu, X., Hamar, P., Trifonova, R., Charisse, K., Manoharan, M., Kirchhausen, T., & Lieberman, J. (2015) · Nature Biotechnology · doi:10.1038/nbt.3298 · Cited by 693 · see citing works
Self-citationMicrofluidic Synthesis of Highly Potent Limit-size Lipid Nanoparticles for In Vivo Delivery of siRNA
Belliveau, N. M., Huft, J., Lin, P. J., Chen, S., Leung, A. K., Leaver, T. J., Wild, A. W., Lee, J. B., Taylor, R. J., Tam, Y. K., et al. (2012) · Molecular Therapy - Nucleic Acids · doi:10.1038/mtna.2012.28 · Cited by 685 · see citing works
Progress towards in Vivo Use of siRNAs
Behlke, M. A. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.01.001 · Cited by 677 · see citing works
siRNA vs. shRNA: Similarities and differences
Rao, D. D., Vorhies, J. S., Senzer, N. N., & Nemunaitis, J. J. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.04.004 · Cited by 658 · 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
siRNA delivery systems for cancer treatment
Oh, Y., & Park, T. G. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.04.018 · Cited by 641 · see citing works
Lipid-based Nanoparticles for Nucleic Acid Delivery
Li, W., & Szoka, F. C. (2007) · Pharmaceutical Research · doi:10.1007/s11095-006-9180-5 · Cited by 642 · see citing works
Frank-Kamenetsky, M. D., Grefhorst, A., Anderson, N. N., Racie, T., Bramlage, B., Akinc, A., Butler, D., Charissé, K., Dorkin, J. R., Fan, Y., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805434105 · Cited by 635 · 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
Sato, Y., Murase, K., Kato, J., Kobune, M., Sato, T., Kawano, Y., Takimoto, R., Takada, K., Miyanishi, K., Matsunaga, T., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1396 · Cited by 610 · see citing works
The importance of nanoparticle shape in cancer drug delivery
Truong, N. P., Whittaker, M. R., Mak, C. W., & Davis, T. P. (2015) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.950564 · Cited by 594 · 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
Lipid nanoparticles enabling gene therapies: from concepts to clinical utility
Kulkarni, J. A., Cullis, P. R., & van der Meel, R. (2018) · Nucleic Acid Therapeutics · doi:10.1089/nat.2018.0721 · Cited by 592 · see citing works
Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation
Aouadi, M., Tesz, G. J., Nicoloro, S. M. C., Wang, M., Chouinard, M., Soto, E. R., Ostroff, G. R., & Czech, M. (2009) · Nature · doi:10.1038/nature07774 · Cited by 572 · see citing works
Wang, H.-X., Li, M., Lee, C. M., Chakraborty, S., Kim, H.-W., Bao, G., & Leong, K. W. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00799 · Cited by 560 · see citing works
Kedmi, R., Ben-Arie, N., & Peer, D. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.05.027 · Cited by 546 · see citing works
microRNAs and the immune response
Lindsay, M. A. (2008) · Trends in Immunology · doi:10.1016/j.it.2008.04.004 · Cited by 532 · see citing works
Huang, H., Sun, F., Owen, D. M., Li, W., Chen, Y., Gale, M., & Ye, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700760104 · Cited by 533 · see citing works
Lipid 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
Human laminopathies: nuclei gone genetically awry
Capell, B. C., & Collins, F. S. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1906 · Cited by 515 · 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
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
Molecular Mechanisms and Biological Functions of siRNA
Dana, H., Chalbatani, G. M., Mahmoodzadeh, H., Gharagouzloo, E., Karimloo, R., Rezaiean, O., Moradzadeh, A., Mazraeh, A., Marmari, V., Rashno, M. M., et al. (2017) · International Journal of Biomedical Science · doi:10.59566/ijbs.2017.13048 · Cited by 507 · see citing works
Targeting kidney mesangium by nanoparticles of defined size
Choi, C. H. J., Zuckerman, J. E., Webster, P. C., & Davis, M. E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103573108 · Cited by 503 · see citing works
Nonviral delivery of synthetic siRNAs in vivo
Akhtar, S., & Benter, I. F. (2007) · Journal of Clinical Investigation · doi:10.1172/jci33494 · Cited by 464 · see citing works
Lipid-based systemic delivery of siRNA
Tseng, Y.-C., Mozumdar, S., & Huang, L. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.03.003 · Cited by 463 · see citing works
Cellular Determinants of Hepatitis C Virus Assembly, Maturation, Degradation, and Secretion
Gastaminza, P., Cheng, G., Wieland, S. F., Zhong, J., Liao, W., & Chisari, F. V. (2007) · Journal of Virology · doi:10.1128/jvi.02053-07 · Cited by 463 · see citing works
A 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
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
Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease
Adams, D., Koike, H., Slama, M., & Coelho, T. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0210-4 · Cited by 450 · see citing works
Liposomal siRNA nanocarriers for cancer therapy
Özpolat, B., Sood, A. K., & Lopez‐Berestein, G. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2013.12.008 · Cited by 445 · see citing works
Microfluidic formulation of nanoparticles for biomedical applications
Shepherd, S. J., Issadore, D., & Mitchell, M. J. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120826 · Cited by 448 · see citing works
DeVincenzo, J. P., Lambkin‐Williams, R., Wilkinson, T. M. A., Cehelsky, J. E., Nochur, S., Walsh, E. E., Meyers, R. E., Gollob, J., & Vaishnaw, A. K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912186107 · Cited by 440 · see citing works
Woodrow, K. A., Cu, Y., Booth, C. J., Saucier-Sawyer, J. K., Wood, M. J., & Saltzman, W. M. (2009) · Nature Materials · doi:10.1038/nmat2444 · Cited by 437 · see citing works
New Generation of Multifunctional Nanoparticles for Cancer Imaging and Therapy
Park, K., Lee, S., Kang, E., Kim, K., Choi, K., & Kwon, I. C. (2009) · Advanced Functional Materials · doi:10.1002/adfm.200801655 · Cited by 430 · 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
Mechanisms and strategies for effective delivery of antisense and siRNA oligonucleotides
Juliano, R. L., Alam, M. R., Dixit, V., & Kang, H. M. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn342 · Cited by 430 · see citing works
Pharmacology of Antisense Drugs
Bennett, C. F., Baker, B. F., Pham, N. C., Swayze, E. E., & Geary, R. S. (2016) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104846 · Cited by 429 · see citing works
Cationic lipids and polymers mediated vectors for delivery of siRNA
Zhang, S., Zhao, B., Jiang, H., Wang, B., & Ma, B. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.07.016 · Cited by 421 · see citing works
Perspectives and opportunities for nanomedicine in the management of atherosclerosis
Lobatto, M. E., Fuster, V., Fayad, Z. A., & Mulder, W. J. M. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3578 · Cited by 423 · see citing works
Principles and effects of microRNA-mediated post-transcriptional gene regulation
Engels, B., & Hutvágner, G. (2006) · Oncogene · doi:10.1038/sj.onc.1209909 · Cited by 410 · see citing works
Cytokines as biomarkers of nanoparticle immunotoxicity
Elsabahy, M., & Wooley, K. L. (2013) · Chemical Society Reviews · doi:10.1039/c3cs60064e · Cited by 408 · see citing works
Development of a novel endosomolytic diblock copolymer for siRNA delivery
Convertine, A. J., Benoit, D. S. W., Duvall, C. L., Hoffman, A. S., & Stayton, P. S. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.10.004 · Cited by 407 · see citing works
Sun, T., Du, J., Yao, Y., Mao, C., Dou, S., Huang, S., Zhang, P., Leong, K. W., Song, E., & Wang, J. (2011) · ACS Nano · doi:10.1021/nn103349h · Cited by 406 · 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
MicroRNAs in Disease and Potential Therapeutic Applications
Soifer, H. S., Rossi, J. J., & Sætrom, P. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300311 · Cited by 395 · see citing works
Gene therapy progress and prospects: non-viral gene therapy by systemic delivery
Li, S.-D., & Huang, L. (2006) · Gene Therapy · doi:10.1038/sj.gt.3302838 · Cited by 392 · 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
Liposomal Delivery Systems: Design Optimization and Current Applications
Lila, A. S. A., & Ishida, T. (2016) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b16-00624 · Cited by 386 · see citing works
Shedding Light on Extracellular Vesicle Biogenesis and Bioengineering
Teng, F., & Fussenegger, M. (2020) · Advanced Science · doi:10.1002/advs.202003505 · Cited by 384 · 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
Heidel, J. D., Yu, Z., Liu, J. Y.-C., Rele, S. M., Liang, Y., Zeidan, R. K., Kornbrust, D. J., & Davis, M. E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701458104 · Cited by 382 · see citing works
Kortylewski, M., Swiderski, P. M., Herrmann, A., Wang, L., Kowolik, C. M., Kujawski, M., Lee, H., Scuto, A., Liu, Y., Yang, C., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt.1564 · Cited by 378 · 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
- Authors
- Zimmermann, T. S., Lee, A. C. H., Akinc, A., Bramlage, B., Bumcrot, D., Fedoruk, M. N., Harborth, J., Heyes, J. A., Jeffs, L. B., John, M., Judge, A. D., Lam, K., McClintock, K., Nechev, L. V., Palmer, L. R., Racie, T., Röhl, I., Seiffert, S., Shanmugam, S., Sood, V., Soutschek, J., Toudjarska, I., Wheat, A. J., Yaworski, E., Zedalis, W., Koteliansky, V., Manoharan, M., Vornlocher, H.-P., & MacLachlan, I.
- Affiliations
- Alnylam Pharmaceuticals (United States) (US)
- Electronic Arts (Canada) (CA)
- Corresponding author
- Zimmermann, Tracy S.
- MacLachlan, Ian
- ORCID
- Venue
- Nature
- Published
- 2006-03-26
- Volume
- 441
- Issue
- 7089
- Pages
- 111-114
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2095151181
- Cited by
- 1,357
- References
- 20
- Citations by year
- 2026: 21 · 2025: 22 · 2024: 30 · 2023: 42 · 2022: 40 · 2021: 35 · 2020: 35 · 2019: 46 · 2018: 30 · 2017: 47 · 2016: 54 · 2015: 70 · 2014: 97 · 2013: 113 · 2012: 111
- FWCI
- 46.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Alnylam Pharmaceuticals
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- RNA interference, gene silencing, siRNA, apolipoprotein B, siRNA therapeutics, systemic siRNA delivery, Macaca fascicularis, non-human primates, hypercholesterolemia, LDL cholesterol, B-cell lymphoma, CARD11
- MeSH terms
- Animals, Apolipoproteins B, Phenotype, Primates, RNA, Messenger, RNA Interference, RNA, Small Interfering
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