Cited by 1,357RNA Interference and Gene DeliveryVirus-based gene therapy researchRNA Research and Splicing

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RNAi-mediated gene silencing in non-human primates

Zimmermann, Tracy S., Lee, Amy C. H., Akinc, Akin, Bramlage, Birgit, Bumcrot, David, Fedoruk, Matthew N., Harborth, Jens, Heyes, James A., Jeffs, Lloyd B., John, Matthias, Judge, Adam D., Lam, Kieu, McClintock, Kevin, Nechev, Lubomir V., Palmer, Lorne R., Racie, Timothy, Röhl, Ingo, Seiffert, Stephan, Shanmugam, Sumi, Sood, Vandana, Soutschek, Jürgen, Toudjarska, Ivanka, Wheat, Amanda J., Yaworski, Ed, Zedalis, William, Koteliansky, Victor, Manoharan, Muthiah, Vornlocher, Hans-Peter, MacLachlan, Ian·2006·Nature

DOI 10.1038/nature04688

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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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Brown, M. S., & Goldstein, J. L. (1986) · Science · doi:10.1126/science.3513311 · Cited by 5,703
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
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
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 2,206
Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7
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 1,261
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 1,260
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 1,175
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 1,027
The RNAi revolution
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Inhibition of respiratory viruses by nasally administered siRNA
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Background
Strategies and Advances in Nanomedicine for Targeted siRNA Delivery
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O'Sullivan, G. J., O’Tuathaigh, C. M. P., Clifford, J. J., O’Meara, G. F., Croke, D. T., & Waddington, J. L. (2006) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2006.06.005 · Cited by 22
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Zhang, Y., Bartz, R., Grigoryan, G., Bryant, M., Aaronson, J., Beck, S., Innocent, N., Klein, L., Procopio, W., Tucker, T., et al. (2015) · ACS Chemical Biology · doi:10.1021/cb500759p · Cited by 23
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Oliveira, C. L., Silveira, I., Veiga, F., & Ribeiro, A. J. (2014) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.945421 · Cited by 23
“Despite detailed studies in preclinical models [87], the ApoB-stable nucleic acid lipid particles (SNALP) developed to treat hyperlipidemia induced a significant immune response in one patient at the highest dose in the Phase I trial and the study has been terminated [88].”
Background
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Khelghati, N., Mokhtarvand, J. S., Mir, M., Alemi, F., Asemi, Z., Sadeghpour, A., Maleki, M., Kafil, H. S., Jadidi‐Niaragh, F., Majidinia, M., et al. (2021) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13824 · Cited by 23
Liposomally encapsulated CDC20 siRNA inhibits both solid melanoma tumor growth and spontaneous growth of intravenously injected melanoma cells on mouse lung
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“Ever since sequence-specific posttranscriptional gene silencing by RNA interference (RNAi) in cultured mammalian cells and in mammals was disclosed in the beginning of the present century [1, 2], studies aimed at demonstrating the therapeutic potential of small interfering RNAs (siRNAs) are being reported in mouse mod…”
Lipid nanoparticle purification by Spin Centrifugation–Dialysis (SCD): A facile and high-throughput approach for small scale preparation of siRNA–lipid complexes
Mihaila, R., Chang, S. D., Wei, A. T., Hu, Z. Y., Ruhela, D., Shadel, T. R., Duenwald, S., Payson, E., Cunningham, J. J., Kuklin, N. A., et al. (2011) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2011.08.017 · Cited by 23
Development of Lipoprotein(a) siRNAs for Mechanism of Action Studies in Non-Human Primate Models of Atherosclerosis
Tadin‐Strapps, M., Robinson, M., LeVoci, L., Andrews, L. E., Yendluri, S., Williams, S., Bartz, S., & Johns, D. G. (2015) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-014-9605-1 · Cited by 23
“We and the others have demonstrated that LNP- siRNAs are effective tools for knockdown of target genes in the liver across a number of preclinical species [12, 16, 26].”
New paradigms on siRNA local application
Pan, M. L., Ni, J., He, H., Gao, S., & Duan, X. (2015) · BMB Reports · doi:10.5483/bmbrep.2015.48.3.089 · Cited by 23
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Allele dependent silencing of COL1A2 using small interfering RNAs
Lindahl, K., Rubin, C., Kindmark, A., & Ljunggren, Ö. (2008) · International Journal of Medical Sciences · doi:10.7150/ijms.5.361 · Cited by 23
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Background
Design of Highly Potent Lipid-Functionalized Peptidomimetics for Efficient in Vivo siRNA Delivery
Xiao, H. T., Altangerel, A., Gerile, G., Wu, Y., & Baigude, H. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5b12144 · Cited by 23
Novel Endosomolytic Poly(amido amine) Polymer Conjugates for Systemic Delivery of siRNA to Hepatocytes in Rodents and Nonhuman Primates
Parmar, R. G., Poslusney, M., Busuek, M., Williams, J. M., Garbaccio, R. M., Leander, K. R., Walsh, E. S., Howell, B. J., Sepp‐Lorenzino, L., Riley, S., et al. (2014) · Bioconjugate Chemistry · doi:10.1021/bc400527e · Cited by 23
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Attarwala, H. Z., Han, M., Kim, J., & Amiji, M. M. (2017) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1478 · Cited by 24
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Lin, Z., Bao, M., Yu, Z., Xue, L., Ju, C., & Zhang, C. (2019) · Biomaterials Science · doi:10.1039/c9bm00494g · Cited by 23
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Dutta, K., Bochicchio, D., Ribbe, A. E., Alfandari, D., Mager, J., Pavan, G. M., & Thayumanavan, S. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b04731 · Cited by 23
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Jebelli, A., Baradaran, B., Mosafer, J., Baghbanzadeh, A., Mokhtarzadeh, A., & Tayebi, L. (2020) · Medicinal Research Reviews · doi:10.1002/med.21735 · Cited by 23
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Reprint of: Nanoparticles for ex vivo siRNA delivery to dendritic cells for cancer vaccines: Programmed endosomal escape and dissociation.
Akita, H., Kogure, K., Moriguchi, R., Nakamura, Y., Higashi, T., Nakamura, T., Serada, S., Fujimoto, M., Naka, T., Futaki, S., et al. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.08.023 · Cited by 94
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“Subsequently, these data were confirmed in nonhuman primates [87].”
Background
Enhancing siRNA delivery by employing lipid nanoparticles
Hope, M. J. (2014) · Therapeutic Delivery · doi:10.4155/tde.14.37 · Cited by 22
“Programmed packaging” for gene delivery
Hyodo, M., Sakurai, Y., Akita, H., & Harashima, H. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.04.023 · Cited by 23
“A large variety of delivery materials, including polymers [22], liposomes [23-25], micelles [26], peptides [27] and proteins [28], are currently under development, in attempts to overcome these obstacles associated with in vivo siRNA delivery.”
Background
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“Numerous studies on therapeutic oligonucleotide delivery efﬁciency, toxicity, and half-life activity in mice and non-human primate models indicated that SNALPs are promising nanoparticles [115–118].”
Background
Nano-Drug Delivery Systems Targeting CAFs: A Promising Treatment for Pancreatic Cancer
Wang, M., Xue, W., Yuan, H., Wang, Z., & Yu, L. (2024) · International Journal of Nanomedicine · doi:10.2147/ijn.s451151 · Cited by 24
“202 Furthermore, nanoparticle-based systems present opportunities for both direct and indirect immune modulation in pancreatic cancer.”
Background
Anticancer Use of Nanoparticles as Nucleic Acid Carriers
Gözüaçık, D., Acar, H. F. Y., Akkoç, Y., Koşar, A., Ekici, I. D., & Eki̇ci̇, S. (2014) · Journal of Biomedical Nanotechnology · doi:10.1166/jbn.2014.1935 · Cited by 22
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Svensson, R. U., Shey, M. R., Ballas, Z. K., Dorkin, J. R., Goldberg, M. S., Akinc, A., Langer, R., Anderson, D. G., Bumcrot, D. A., & Henry, M. D. (2008) · Molecular Therapy · doi:10.1038/mt.2008.187 · Cited by 22
siRNA Delivery for the treatment of ovarian cancer
Goldberg, M. S. (2013) · Methods · doi:10.1016/j.ymeth.2013.01.007 · Cited by 22
Lipid-Coated Calcium Phosphate Nanoparticles for Nonviral Gene Therapy
Haynes, M. T., & Huang, L. (2014) · Advances in genetics · doi:10.1016/b978-0-12-800148-6.00007-9 · Cited by 21
Advances in Lipid-Based Platforms for RNAi Therapeutics
Falsini, S., Ciani, L., Ristori, S., Fortunato, A., & Arcangeli, A. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400791q · Cited by 23
Recent advances in the targeting of systemically administered non-viral gene delivery systems
Khalil, I. A., Sato, Y., & Harashima, H. (2019) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2019.1656196 · Cited by 22
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Mihaila, R., Ruhela, D., Keough, E., Cherkaev, E., Chang, S. D., Galinski, B., Bartz, R., Brown, D., Howell, B. J., & Cunningham, J. J. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2017.04.003 · Cited by 22
“degradation of siRNA in the cytoplasm; (6) formation of active RISC with target mRNA; (7) cleavage of target mRNA by RISC; (8) transcription rate (of mRNA); and (9)”
Background
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A review of antisense therapeutic interventions for molecular biological targets in asthma.
Popescu, F., & Popescu, F. (2007) · PubMed · Cited by 22
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“Notable milestones include the silencing of the hepatitis B virus and APOB [131] via siRNAs in preclinical animal studies, as well as the recent approval of patisiran [132]—an siRNA administered in an LNP formulation.”
Reflections on Alnylam
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Lipid‐based nucleic acid therapeutics with in vivo efficacy
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Wan, J., Bauman, J. A., Graziewicz, M. A., Sazani, P., & Kole, R. (2013) · Cancer treatment and research · doi:10.1007/978-3-642-31659-3_9 · Cited by 22
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Oka, K., Mullins, C. E., Kushwaha, R. S., Leen, A. M., & Chan, L. (2014) · Gene Therapy · doi:10.1038/gt.2014.85 · Cited by 21
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Bhattacharya, S., Alkharfy, K. M., Janardhanan, R., & Mukhopadhyay, D. (2012) · Nanotechnology Reviews · doi:10.1515/ntrev-2011-0010 · Cited by 21
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Background
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Sato, T., Sato, Y., Iwai, K., Kuge, S., Nishizawa, S., & Teramae, N. (2014) · Chemical Communications · doi:10.1039/c4cc08800j · Cited by 21
Oxime Ether Lipids Containing Hydroxylated Head Groups are More Superior siRNA Delivery Agents than their Nonhydroxylated Counterparts
Gupta, K., Mattingly, S. J., Knipp, R. J., Afonin, K. A., Viard, M., Bergman, J. T., Stepler, M., Nantz, M. H., Puri, A., & Shapiro, B. A. (2015) · Nanomedicine · doi:10.2217/nnm.15.105 · Cited by 21
In vivo target validation using gene invalidation, RNA interference and protein functional knockout models: it is the time to combine
Vidalin, O., Muslmani, M., Estienne, C., Echchakir, H., & Abina, A. M. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.06.017 · Cited by 21
Uptake of plasmid-loaded nanoparticles in breast cancer cells and effect on Plk1 expression
Steinhauser, I., Langer, K., Strebhardt, K., & Spänkuch, B. (2009) · Journal of drug targeting · doi:10.1080/10611860903118823 · Cited by 21
“Only a few reports exist which describe the successful introduction of modifications into siRNAs with an in vivo effect (Check, 2005; Zimmermann et al., 2006).”
Background
Nonviral targeted mRNA delivery: principles, progresses, and challenges
He, X., Li, G., Huang, L., Shi, H., Zhong, S., Zhao, S., Jiao, X., Xin, J., Yin, X., Liu, S., et al. (2025) · MedComm · doi:10.1002/mco2.70035 · Cited by 22
“1,2-dilinoleyloxy-N, N-dimethyl-3-aminopropane, as an efficient siRNA delivery material, 118 has been used for the saRNA delivery.”
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“The design of new lipids has been evolving ever since the first proof of concept for ApoB gene silencing using DLinDMA lipid in hepatocytes was achieved [55].”
Background
An update on RNA interference-mediated gene silencing in cancer therapy
Ren, Y., & Zhang, Y. (2014) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2014.935334 · Cited by 20
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Mudd, S. R., Trubetskoy, V. S., Blokhin, A. V., Weichert, J. P., & Wolff, J. A. (2010) · Bioconjugate Chemistry · doi:10.1021/bc900558z · Cited by 20
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Lin, X., Li, L., Wang, R., Wilcox, D. M., Zhao, X. B., Song, J., Huang, X., Hansen, T. M., Dande, P., Wada, C. K., et al. (2011) · RNA · doi:10.1261/rna.2546011 · Cited by 20
“Compared with DODAP-based liposomes, the literature-described Stable Nucleic Acid Lipid Particle (SNALP) (Zimmermann et al. 2006) exhibited a more robust expression of b-galactosidase within the TetR-ODC-LacZ-derived tumors.”
BackgroundMethod
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Akita, H., Fujiwara, T., Santiwarangkool, S., Hossen, M. N., Kajimoto, K., El‐Sayed, A., Tabata, Y., & Harashima, H. (2015) · Small · doi:10.1002/smll.201500909 · Cited by 20
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Kassim, S. H., Wilson, J. M., & Rader, D. J. (2010) · Clinical Lipidology · doi:10.2217/clp.10.73 · Cited by 19
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Yang, N. (2012) · International Journal of Pharmaceutical Investigation · doi:10.4103/2230-973x.104388 · Cited by 20
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Background
Systemic Delivery of Stable siRNA-Encapsulating Lipid Vesicles: Optimization, Biodistribution, and Tumor Suppression
Dar, G. H., Gopal, V., & Rao, N. M. (2014) · Molecular Pharmaceutics · doi:10.1021/mp500677x · Cited by 20
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Szoka, F. C. (2008) · Science · doi:10.1126/science.1154253 · Cited by 20
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“For example, siRNAs to APOB significantly reduced the mRNA expression and plasma apoB-containing lipoprotein concentrations in nonhuman primates [99] .”
Background
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Trubetskoy, V. S., Griffin, J. B., Nicholas, A. L., Nord, E. M., Xu, Z., Peterson, R. M., Wooddell, C. I., Rozema, D. B., Wakefield, D. H., Lewis, D. L., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw828 · Cited by 19
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Kim, D. H., & Rossi, J. J. (2009) · Current Protocols in Nucleic Acid Chemistry · doi:10.1002/0471142700.nc1601s36 · Cited by 19
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Li, Y., Zheng, S., Liang, X., Jin, Y., Wu, Y., Bai, H., Liu, R., Dai, Z., Liang, Z., & Shi, T.-J. S. (2014) · Bioconjugate Chemistry · doi:10.1021/bc500414e · Cited by 18
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“First, by developing stable nucleic acid lipid particles (SNALPs) characterized by very efficient RNA encapsulation, small and homogenous size, and >90% effective, long-lasting gene silencing in non-human primates [141].”
Background
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 19
Stimulus-activated ribonuclease targeting chimeras for tumor microenvironment activated cancer therapy
Zhang, Y., Zhu, J., Qiu, L., Lv, Z., Zhao, Z., Ren, X., Guo, Y., Chen, Y., Li, M., Fan, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56691-3 · Cited by 25
Development and clinical applications of siRNA-encapsulated lipid nanoparticles in cancer
Lin, P. J. C., Tam, Y. K., & Cullis, P. R. (2014) · Clinical Lipidology · doi:10.2217/clp.14.27 · Cited by 18
Efficient reduction of serum cholesterol by combining a liver-targeted gene delivery system with chemically modified apolipoprotein B siRNA
Kang, J., Tachibana, Y., Obika, S., Harada‐Shiba, M., & Yamaoka, T. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.08.030 · Cited by 18
Coordinative Amphiphiles as Tunable siRNA Transporters
Kim, J. B., Lee, Y. M., Ryu, J., Lee, E. J., Kim, W. J., Keum, G., & Bang, E. (2016) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.6b00260 · Cited by 18
Enhancement of lung gene delivery after aerosol: a new strategy using non-viral complexes with antibacterial properties
Mottais, A., Gall, T. L., Sibiril, Y., Ravel, J., Laurent, V., d’Arbonneau, F., & Montier, T. (2017) · Bioscience Reports · doi:10.1042/bsr20160618 · Cited by 20
Amphiphilic poly(α)glutamate polymeric micelles for systemic administration of siRNA to tumors
Krivitsky, A., Polyak, D., Scomparin, A., Eliyahu, S., Ofek, P., Tiram, G., Kalinski, H., Avkin-Nachum, S., Feiner‐Gracia, N., Albertazzi, L., et al. (2017) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2017.10.012 · Cited by 18
Delivery of small interfering RNAs by nanovesicles for cancer therapy
Pengnam, S., Plianwong, S., Yingyongnarongkul, B., Patrojanasophon, P., & Opanasopit, P. (2021) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2021.100425 · Cited by 18
Effective small interfering RNA delivery in vitro via a new stearylated cationic peptide
Chen, P., Chen, B., Ran, P., & Askhatova, D. (2015) · International Journal of Nanomedicine · doi:10.2147/ijn.s79306 · Cited by 19
New targets and emerging therapies for reducing LDL cholesterol
Lilly, S. M., & Rader, D. J. (2007) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3282f169c6 · Cited by 18
Phospholipase A2Sensitive Liposomes for Delivery of Small Interfering RNA (siRNA)
Foged, C., Nielsen, H. M., & Frøkjær, S. (2007) · Journal of Liposome Research · doi:10.1080/08982100701530373 · Cited by 18
Sequential intravenous injection of anionic polymer and cationic lipoplex of siRNA could effectively deliver siRNA to the liver
Hattori, Y., Arai, S., Okamoto, R., Hamada, M., Kawano, K., & Yonemochi, E. (2014) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2014.09.059 · Cited by 17
In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs)
Baigude, H., Su, J., McCarroll, J. A., & Rana, T. M. (2013) · ACS Medicinal Chemistry Letters · doi:10.1021/ml4001003 · Cited by 17
Therapeutic gene targeting approaches for the treatment of dyslipidemias and atherosclerosis
Mäkinen, P. I., & Ylä‐Herttuala, S. (2013) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32835da13c · Cited by 17
The application of RNAi-based treatments for inflammatory bowel disease
Olesen, M. T. J., Ballarín-González, B., & Howard, K. A. (2013) · Drug Delivery and Translational Research · doi:10.1007/s13346-013-0156-9 · Cited by 17
Quick identification of effective small interfering RNAs that inhibit the replication of coxsackievirus A16
Wu, Z., GAO, Y., Sun, L., Tien, P., & Jin, Q. (2008) · Antiviral Research · doi:10.1016/j.antiviral.2008.06.017 · Cited by 17
“Many primary in vivo system elivery methods (e.g. liposome-based delivery and viral vectorased delivery) (Morris and Rossi, 2006; Zimmermann et al., 2006) ave been reported recently, but further work should be conducted n vivo to investigate appropriate siRNA delivery strategies. cknowledgements We…”
Background
Enhancing the Pharmacokinetic/Pharmacodynamic Properties of Therapeutic Nucleotides Using Lipid Nanoparticle Systems
Lin, P. J. C., & Tam, Y. K. (2015) · Future Medicinal Chemistry · doi:10.4155/fmc.15.108 · Cited by 18
The oncogenic role of protein kinase D3 in cancer
Liu, Y., Song, H., Zhou, Y., Ma, X., Xu, J., Yu, Z., & Chen, L. (2020) · Journal of Cancer · doi:10.7150/jca.50899 · Cited by 16
“Alternative methods to chemical inhibition could include systemic delivery of siRNA or nucleic acid-based therapies that could allow to specifically target PRKDs [58, 59].”
Method
Emerging therapeutic approaches for peritoneal metastases from gastrointestinal cancers
Sikora, A., Sullivan, K. M., Dineen, S. P., Raoof, M., & Karolak, A. M. (2024) · Molecular Therapy Oncology · doi:10.1016/j.omton.2024.200767 · Cited by 16
“123 Therefore, a novel RNAi-based therapeutic nanoconstruct, DFP-10825, has been investigated.”
Background
Chemical Design Strategy of Ionizable Lipids for In Vivo mRNA Delivery
He, Z., Liu, Z., & Chen, Y. (2024) · ChemMedChem · doi:10.1002/cmdc.202400199 · Cited by 16
Protection against TNFα-dependent liver toxicity by intraperitoneal liposome delivered DsiRNA targeting TNFα in vivo
Lundberg, P. S., Yang, H.-J., Jung, S.-J., Behlke, M. A., Rose, S. D., & Cantin, E. M. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.10.034 · Cited by 16
Therapy for persistent HIV
Keedy, K. S., & Margolis, D. M. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.02.001 · Cited by 16
Effect of biological matrix and sample preparation on qPCR quantitation of siRNA drugs in animal tissues
Seitzer, J. L., Zhang, H., Koser, M. L., Pei, Y., & Abrams, M. T. (2010) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2010.09.005 · Cited by 16
In vivosiRNA delivery of Keap1 modulates death and survival signaling pathways and attenuates Concanavalin A-induced acute liver injury in mice
González‐Rodríguez, Á., Reibert, B., Amann, T., Constien, R., Rondinone, C. M., & Valverde, Á. M. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.015537 · Cited by 16
Gene Therapy - Developments and Future Perspectives
Kang, C. (2011) · InTech eBooks · doi:10.5772/748 · Cited by 16
Can modulators of apolipoproteinB biogenesis serve as an alternate target for cholesterol-lowering drugs?
Doonan, L. M., Fisher, E. A. A., & Brodsky, J. L. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2018.03.010 · Cited by 17
An RNAi therapeutic, DFP-10825, for intraperitoneal and intrapleural malignant cancers
Ando, H., & Ishida, T. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.08.002 · Cited by 17
Allele Dependent Silencing of Collagen Type I Using Small Interfering RNAs Targeting 3'UTR Indels - a Novel Therapeutic Approach in Osteogenesis Imperfecta
Lindahl, K., Kindmark, A., Laxman, N., Åström, E., Rubin, C., & Ljunggren, Ö. (2013) · International Journal of Medical Sciences · doi:10.7150/ijms.5774 · Cited by 16
“Since these original discoveries the rules determining successful mRNA suppression by siRNAs have been extensively studied and siRNAs are now invaluable tools for studies of partial gene knockout in vitro as well as in vivo[14].”
Background
An in vivo evaluation of amphiphilic, biodegradable peptide copolymers as siRNA delivery agents
Barrett, S. E., Abrams, M. T., Burke, R. S., Carr, B., Crocker, L. S., Garbaccio, R. M., Howell, B. J., Kemp, E. A., Kowtoniuk, R. A., Latham, A. H., et al. (2014) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2014.03.011 · Cited by 16
RNA interference against polo-like kinase-1 in advanced non-small cell lung cancers
Kawata, E., Ashihara, E., & Maekawa, T. (2011) · Journal of Clinical Bioinformatics · doi:10.1186/2043-9113-1-6 · Cited by 19
“Recently a lot of useful non-viral DDSs for small interfering RNAs (siRNAs) have been developed [11-17].”
Background
Temperature and pH sensitivity of a stabilized self-nanoemulsion formed using an ionizable lipid-like material via an oil-to-surfactant transition
Tanaka, 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
Locked Nucleic Acid: Properties and Therapeutic Aspects
Koch, T., Rosenbohm, C., Hansen, H. F., Hansen, B. R., Straarup, E. M., & Kauppinen, S. (2008) · Royal Society of Chemistry eBooks · doi:10.1039/9781847558275-00103 · Cited by 16
Systemic Delivery of Small RNA Using Lipid Nanoparticles
Asai, T., & Oku, N. (2014) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.13-00744 · Cited by 15

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: Lee, Amy C. H.
Fedoruk, Matthew N.
Harborth, Jens
Heyes, James A.
Lam, Kieu
McClintock, Kevin
Palmer, Lorne R.
Manoharan, Muthiah
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2006-03-26
Volume: 441
Issue: 7089
Pages: 111-114
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature04688
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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RNAi-mediated gene silencing in non-human primates

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