GalNAc-siRNA conjugates: leading the way for delivery of RNAi therapeutics
Open accessAbstract
Short-interfering RNA (siRNA)-induced RNAi responses have great potential to treat a wide variety of human diseases from cancer to pandemic viral outbreaks to Parkinson's Disease. However, before siRNAs can become drugs, they must overcome a billion years of evolutionary defenses designed to keep invading RNAs on the outside cells from getting to the inside of cells. Not surprisingly, significant effort has been placed in developing a wide array of delivery technologies. Foremost of these has been the development of N-acetylgalactosamine (GalNAc) siRNA conjugates for delivery to liver. Tris-GalNAc binds to the Asialoglycoprotein receptor that is highly expressed on hepatocytes resulting in rapid endocytosis. While the exact mechanism of escape across the endosomal lipid bilayer membrane remains unknown, sufficient amounts of siRNAs enter the cytoplasm to induce robust, target selective RNAi responses in vivo. Multiple GalNAc-siRNA conjugate clinical trials, including two phase III trials, are currently underway by three biotech companies to treat a wide variety of diseases. GalNAc-siRNA conjugates are a simple solution to the siRNA delivery problem for liver hepatocytes and have shown the RNAi (and antisense oligonucleotide) field the path forward for targeting other tissue types.
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GalNAc-siRNA conjugates achieve systemic stability against nucleases, improving pharmacokinetics.
“Results showed that by conjugating the engineered ASGPR ligand to the chemically modified siRNA molecule, GalNAc-siRNA conjugates could achieve systemic stability against nucleases, which would in turn improve pharmacokinetics.”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [78]
Single or multiple low-volume subcutaneous injections of GalNAc-siRNA conjugates resulted in effective suppression of the target gene in the liver.
“Most importantly, single or multiple low-volume subcutaneous injections of these conjugates resulted in effective suppression of the target gene in the liver.[51, 77, 78]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [78]
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Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C. (1998) · Nature · doi:10.1038/35888 · Cited by 15,429 · see citing works
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456 · see citing works
RNAi-mediated gene silencing in non-human primates
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., et al. (2006) · Nature · doi:10.1038/nature04688 · Cited by 1,357 · see citing works
The chemical evolution of oligonucleotide therapies of clinical utility
Khvorova, A., & Watts, J. K. (2017) · Nature Biotechnology · doi:10.1038/nbt.3765 · Cited by 1,216 · see citing works
Nair, J. K., Willoughby, J. L. S., Chan, A., Charisse, K., Alam, M. R., Wang, Q., Hoekstra, M., Kandasamy, P., Kel’in, A. V., Milstein, S., et al. (2014) · Journal of the American Chemical Society · doi:10.1021/ja505986a · Cited by 1,141 · see citing works
Overcoming cellular barriers for RNA therapeutics
Dowdy, S. F. (2017) · Nature Biotechnology · doi:10.1038/nbt.3802 · Cited by 1,139 · see citing works
Self-citationThe role of sialic acid in determining the survival of glycoproteins in the circulation
Morell, A. G., Gregoriadis, G., Scheinberg, I. H., Hickman, J., & Ashwell, G. (1971) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)76994-4 · Cited by 1,072 · see citing works
Passenger-Strand Cleavage Facilitates Assembly of siRNA into Ago2-Containing RNAi Enzyme Complexes
Matranga, C., Tomari, Y., Shin, C., Bartel, D. P., & Zamore, P. D. (2005) · Cell · doi:10.1016/j.cell.2005.08.044 · Cited by 969 · see citing works
The delivery of therapeutic oligonucleotides
Juliano, R. L. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw236 · Cited by 863 · see citing works
Receptor-mediated in vitro gene transformation by a soluble DNA carrier system.
Wu, G. Y., & Wu, C. H. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61209-8 · Cited by 855 · see citing works
Geuze, H. J., Slot, J. W., Strous, G. J., Lodish, H. F., & Schwartz, A. L. (1983) · Cell · doi:10.1016/0092-8674(83)90518-4 · Cited by 816 · see citing works
A highly durable RNAi therapeutic inhibitor of PCSK9
Fitzgerald, K., White, S., Borodovsky, A., Bettencourt, B. R., Strahs, A., Clausen, V., Wijngaard, P., Horton, J. D., Taubel, J., Brooks, A., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1609243 · Cited by 768 · see citing works
The Crystal Structure of Human Argonaute2
Schirle, N. T., & MacRae, I. J. (2012) · Science · doi:10.1126/science.1221551 · Cited by 697 · 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
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
Receptor-mediated gene delivery and expression in vivo.
Wu, G. Y., & Wu, C. H. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68081-0 · Cited by 636 · see citing works
Asialoglycoprotein receptor mediated hepatocyte targeting — Strategies and applications
D’souza, A. A., & Devarajan, P. V. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.02.022 · Cited by 624 · see citing works
Prakash, T. P., Graham, M. J., Yu, J., Carty, R., Low, A., Chappell, A. E., Schmidt, K., Zhao, C., Aghajan, M., Murray, H. F., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku531 · Cited by 616 · see citing works
Carbohydrates in Chemistry and Biology
Ernst, B., Hart, G. W., & Sînaÿ, P. (2000) · Wiley eBooks · doi:10.1002/9783527618255 · Cited by 597 · see citing works
Structural basis for microRNA targeting
Schirle, N. T., Sheu‐Gruttadauria, J., & MacRae, I. J. (2014) · Science · doi:10.1126/science.1258040 · Cited by 563 · see citing works
Lee, Y. C., Townsend, R. R., Hardy, M. R., Lönngren, J., Arnarp, J., Haraldsson, M., & Lönn, H. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)33240-x · Cited by 503 · see citing works
Wall, D. A., Wilson, G., & Hubbard, A. L. (1980) · Cell · doi:10.1016/0092-8674(80)90116-6 · Cited by 484 · see citing works
Ryter, J. M., & Schultz, S. C. (1998) · The EMBO Journal · doi:10.1093/emboj/17.24.7505 · Cited by 479 · see citing works
Physical and Chemical Studies on Ceruloplasmin
Morell, A. G., Irvine, R. A., Sternlieb, I., Scheinberg, I. H., & Ashwell, G. (1968) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99337-3 · Cited by 477 · see citing works
Robbins, M., Judge, A. D., & MacLachlan, I. (2009) · Oligonucleotides · doi:10.1089/oli.2009.0180 · Cited by 453 · see citing works
Hepatic Drug Targeting: Phase I Evaluation of Polymer-Bound Doxorubicin
Seymour, L. W., Ferry, D. R., Anderson, D., Hesslewood, S., Julyan, P. J., Poyner, R., Doran, J., Young, A., Burtles, S. S., & Kerr, D. J. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.20.6.1668 · Cited by 435 · see citing works
Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy
Pasi, J., Rangarajan, S., Georgiev, P., Mant, T., Creagh, M. D., Lissitchkov, T. J., Bevan, D. H., Austin, S. K., Hay, C. R. M., Hegemann, I., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1616569 · Cited by 369 · see citing works
Schwartz, A. L., Fridovich, S. E., & Lodish, H. F. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34710-0 · Cited by 368 · see citing works
The Binding of Desialylated Glycoproteins by Plasma Membranes of Rat Liver
Pricer, W. E., & Ashwell, G. (1971) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)62010-1 · Cited by 362 · see citing works
Plank, C., Zatloukal, K., Cotten, M. L., Mechtler, K., & Wagner, E. (1992) · Bioconjugate Chemistry · doi:10.1021/bc00018a012 · Cited by 324 · see citing works
Sehgal, A., Barros, S. A., Ivanciu, L., Cooley, B. C., Qin, J., Racie, T., Hettinger, J. L., Carioto, M., Jiang, Y., Brodsky, J., et al. (2015) · Nature Medicine · doi:10.1038/nm.3847 · Cited by 307 · see citing works
Preclinical and Clinical Advances of GalNAc-Decorated Nucleic Acid Therapeutics
Huang, Y. (2016) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2016.12.003 · Cited by 295 · see citing works
Hepatocyte-targeted RNAi Therapeutics for the Treatment of Chronic Hepatitis B Virus Infection
Wooddell, C. I., Rozema, D. B., Hoßbach, M., John, M., Hamilton, H., Chu, Q., Hegge, J., Klein, J. J., Wakefield, D. H., Oropeza, C. E., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2013.31 · Cited by 291 · see citing works
Hepatic Drug Targeting: Phase I Evaluation of Polymer-Bound Doxorubicin
Seymour, L. W., Ferry, D. R., Anderson, D., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.20.6.1668 · Cited by 287 · see citing works
Wu, C. H., Wilson, J. M., & Wu, G. Y. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)71447-6 · Cited by 286 · see citing works
Steer, C. J., & Ashwell, G. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85843-x · Cited by 274 · see citing works
Salomon, W. E., Jolly, S. M., Moore, M. J., Zamore, P. D., & Serebrov, V. (2015) · Cell · doi:10.1016/j.cell.2015.06.029 · Cited by 266 · see citing works
The response of mammalian cells to double-stranded RNA
Gantier, M. P., & Williams, B. R. G. (2007) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2007.06.016 · Cited by 266 · see citing works
Tanabe, T., Pricer, W. E., & Ashwell, G. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34164-9 · Cited by 263 · see citing works
Baenziger, J., & Fiete, D. (1980) · Cell · doi:10.1016/0092-8674(80)90371-2 · Cited by 248 · see citing works
Evolving landscape in the management of transthyretin amyloidosis
Hawkins, P. N., Ando, Y., Dispenzeri, A., González‐Duarte, A., Adams, D., & Suhr, O. B. (2015) · Annals of Medicine · doi:10.3109/07853890.2015.1068949 · Cited by 243 · see citing works
Matsuda, S., Keiser, K., Nair, J. K., Charissé, K., Manoharan, R. M., Kretschmer, P., Peng, C. G., Kel’in, A. V., Pachamuthu, K., Willoughby, J. L. S., et al. (2015) · ACS Chemical Biology · doi:10.1021/cb501028c · Cited by 222 · see citing works
Evidence for targeted gene delivery to Hep G2 hepatoma cells in vitro
Wu, G. Y., & Wu, C. H. (1988) · Biochemistry · doi:10.1021/bi00403a008 · Cited by 222 · see citing works
Progress Toward In Vivo Use of siRNAs-II
Rettig, G. R., & Behlke, M. A. (2011) · Molecular Therapy · doi:10.1038/mt.2011.263 · Cited by 217 · see citing works
Clinical Proof of Concept for a Novel Hepatocyte-Targeting GalNAc-siRNA Conjugate
Zimmermann, T. S., Karsten, V., Chan, A., Chiesa, J., Boyce, M. J., Bettencourt, B. R., Hutabarat, R. M., Nochur, S. V., Vaishnaw, A. K., & Gollob, J. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2016.10.019 · Cited by 216 · see citing works
Physical and Chemical Studies on Ceruloplasmin
Morell, A. G., den Hamer, C. J. A. V., Scheinberg, I. H., & Ashwell, G. (1966) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99835-2 · Cited by 209 · see citing works
Liebow, A., Li, X., Racie, T., Hettinger, J. L., Bettencourt, B. R., Najafian, N., Haslett, P. A. J., Fitzgerald, K. J., Holmes, R. P., Erbe, D. V., et al. (2016) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016030338 · Cited by 200 · see citing works
Meier, M., Bider, M. D., Malashkevich, V. N., Spiess, M., & Burkhard, P. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3853 · Cited by 192 · see citing works
Rajeev, K. G., Nair, J. K., Jayaraman, M., Charissé, K., Taneja, N., O′Shea, J., Willoughby, J. L. S., Yucius, K., Nguyen, T. M., Shulga‐Morskaya, S., et al. (2015) · ChemBioChem · doi:10.1002/cbic.201500023 · Cited by 185 · see citing works
Physical and Chemical Studies on Ceruloplasmin
den Hamer, C. J. A. V., Morell, A. G., Scheinberg, I. H., Hickman, J. W., & Ashwell, G. (1970) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)63808-1 · Cited by 183 · see citing works
Wu, G. Y., & Wu, C. H. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42295-8 · Cited by 182 · see citing works
Subcellular distribution of a mammalian hepatic binding protein specific for asialoglycoproteins.
Pricer, W. E., & Ashwell, G. (1976) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32884-3 · Cited by 180 · see citing works
Fate of receptor and ligand during endocytosis of asialoglycoproteins by isolated hepatocytes.
Bridges, K. R., Harford, J. B., Ashwell, G., & Klausner, R. D. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.2.350 · Cited by 175 · see citing works
Stockert, R. J., Morell, A. G., & Scheinberg, I. H. (1974) · Science · doi:10.1126/science.186.4161.365 · Cited by 169 · see citing works
Gouya, L., Ventura, P., Balwani, M., Bissell, D. M., Rees, D. C., Stölzel, U., Phillips, J. D., Kauppinen, R., Langendonk, J. G., Desnick, R. J., et al. (2019) · Hepatology · doi:10.1002/hep.30936 · Cited by 168 · see citing works
Catabolism of Desialylated Ceruloplasmin in the Liver
Gregoriadis, G. C., Morell, A. G., Sternlieb, I., et al. (1970) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)62728-0 · Cited by 163 · see citing works
Hepatic uptake of proteins coupled to fetuin glycopeptide
Rogers, J. C., & Kornfeld, S. A. (1971) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(71)90462-1 · Cited by 158 · see citing works
Physical and Chemical Studies on Ceruloplasmin
Hickman, J. W., Ashwell, G., Morell, A. G., et al. (1970) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)63329-0 · Cited by 146 · see citing works
Parmar, R. G., Willoughby, J. L. S., Liu, J., Foster, D. J., Brigham, B., Theile, C. S., Charissé, K., Akinc, A., Guidry, E. N., Pei, Y., et al. (2016) · ChemBioChem · doi:10.1002/cbic.201600130 · Cited by 143 · see citing works
The Binding of Desialylated Glycoproteins by Plasma Membranes of Rat Liver
Lenten, L. V., & Ashwell, G. (1972) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)45034-5 · Cited by 142 · see citing works
Sliedregt, L. A. J. M., Rensen, P. C. N., Rump, E. T., van Santbrink, P. J., Bijsterbosch, M. K., Valentijn, A. R. P. M., van der MAREL, G. A., BOOM, J. H. V., van Berkel, T. J. C., & Biessen, E. A. L. (1999) · Journal of Medicinal Chemistry · doi:10.1021/jm981078h · Cited by 139 · see citing works
Grewal, P. K. (2010) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(10)79013-3 · Cited by 136 · see citing works
Prakash, T. P., Yu, J., Migawa, M. T., Kinberger, G. A., Wan, W. B., Østergaard, M. E., Carty, R. L., Vasquez, G., Low, A., Chappell, A. E., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01948 · Cited by 132 · see citing works
Juliano, R. L., Ming, X., Carver, K. A., & Laing, B. M. (2014) · Nucleic Acid Therapeutics · doi:10.1089/nat.2013.0463 · Cited by 130 · see citing works
Chan, A., Liebow, A., Yasuda, M., Gan, L., Racie, T., Maier, M., Kuchimanchi, S., Foster, D., Milstein, S., Charisse, K., et al. (2015) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2015.36 · Cited by 128 · see citing works
Difficulties in the quantification of asialoglycoprotein receptors on the rat hepatocyte.
Schwartz, A. L., Rup, D., & Lodish, H. F. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)70522-5 · Cited by 124 · see citing works
Yasuda, M., Gan, L., Chen, B., Kadirvel, S., Yu, C., Phillips, J. D., New, M. I., Liebow, A., Fitzgerald, K. J., Querbes, W., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1406228111 · Cited by 124 · see citing works
Intracellular distribution of DNA internalized through calcium phosphate precipitation
Orrantia, E., & Chang, P. L. (1990) · Experimental Cell Research · doi:10.1016/0014-4827(90)90181-9 · Cited by 118 · see citing works
Preclinical evaluation of RNAi as a treatment for transthyretin-mediated amyloidosis
Butler, J. S., Chan, A., Costelha, S., Fishman, S., Willoughby, J. L. S., Borland, T. D., Milstein, S., Foster, D. J., Gonçalves, P., Chen, Q., et al. (2016) · Amyloid · doi:10.3109/13506129.2016.1160882 · Cited by 113 · see citing works
The binding site of rabbit hepatic lectin.
Sarkar, M., Liao, J., Kabat, E. A., et al. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50739-0 · Cited by 103 · see citing works
Wong, S. C., Klein, J. J., Hamilton, H., Chu, Q., Frey, C. L., Trubetskoy, V. S., Hegge, J., Wakefield, D. H., Rozema, D. B., & Lewis, D. L. (2012) · Nucleic Acid Therapeutics · doi:10.1089/nat.2012.0389 · Cited by 101 · see citing works
Effect of reductive lactosamination on the hepatic uptake of bovine pancreatic ribonuclease A dimer.
Wilson, G. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38039-0 · Cited by 100 · see citing works
Optimized siRNA-PEG Conjugates for Extended Blood Circulation and Reduced Urine Excretion in Mice
Iversen, F., Yang, C., Dagnæs‐Hansen, F., Schaffert, D., Kjems, J., & Gao, S. (2013) · Theranostics · doi:10.7150/thno.5743 · Cited by 98 · see citing works
Disposition and Pharmacology of a GalNAc3-conjugated ASO Targeting Human Lipoprotein (a) in Mice
Yu, R. Z., Graham, M. J., Post, N. M., Riney, S., Zanardi, T. A., Hall, S., Burkey, J., Shemesh, C. S., Prakash, T. P., Seth, P. P., et al. (2016) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2016.26 · Cited by 97 · see citing works
Merwin, J. R., Noell, G. S., Thomas, W. L., Chiou, H. C., DeRome, M., McKee, T. D., Spitalny, G. L., & Findeis, M. A. (1994) · Bioconjugate Chemistry · doi:10.1021/bc00030a017 · Cited by 93 · see citing works
Identification and quantification of the rat hepatocyte asialoglycoprotein receptor.
Schwartz, A. L., Marshak‐Rothstein, A., Rup, D., & Lodish, H. F. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.6.3348 · Cited by 91 · see citing works
Schlegel, M. K., Foster, D. J., Kel’in, A. V., Zlatev, I., Bisbe, A., Jayaraman, M., Lackey, J. G., Rajeev, K. G., Charissé, K., Harp, J. M., et al. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b02694 · Cited by 90 · see citing works
Rensen, P. C. N., van Leeuwen, S. H., Sliedregt, L. A. J. M., van Berkel, T. J. C., & Biessen, E. A. L. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049481d · Cited by 87 · see citing works
Rat hepatocytes bind to synthetic galactoside surfaces via a patch of asialoglycoprotein receptors.
Weigel, P. H. (1980) · The Journal of Cell Biology · doi:10.1083/jcb.87.3.855 · Cited by 86 · see citing works
Endocytosis of asialoglycoprotein-enzyme conjugates by hepatocytes.
Rj, S., Haimes, H. B., Ag, M., et al. (1980) · PubMed · Cited by 84 · see citing works
Targeted delivery of oligodeoxynucleotides to parenchymal liver cells in vivo
Biessen, E. A. L., Vietsch, H., Rump, E. T., Fluiter, K., Kuiper, J., Bijsterbosch, M. K., & van Berkel, T. J. C. (1999) · Biochemical Journal · doi:10.1042/bj3400783 · Cited by 82 · see citing works
Novogrodsky, A., & Ashwell, G. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.2.676 · Cited by 70 · see citing works
FIUME, L., Mattioli, A., Balboni, P. G., Tognon, M. G., Barbanti-Brodano, G., Vries, J. D., & Wieland, T. (1979) · FEBS Letters · doi:10.1016/0014-5793(79)81247-8 · Cited by 66 · see citing works
Hangeland, J. J., Levis, J. T., Lee, Y. C., & Ts’o, P. O. P. (1995) · Bioconjugate Chemistry · doi:10.1021/bc00036a006 · Cited by 63 · see citing works
FIUME, L., Mattioli, A., Busi, C., Balboni, P. G., Barbanti-Brodano, G., Vries, J. D., Altmann, R., & Wieland, T. (1980) · FEBS Letters · doi:10.1016/0014-5793(80)80639-9 · Cited by 61 · see citing works
Intracellular Localization and Routing of miRNA and RNAi Pathway Components
Ohrt, T., Muetze, J., Svoboda, P., & Schwille, P. (2012) · Current Topics in Medicinal Chemistry · doi:10.2174/156802612798919132 · Cited by 59 · see citing works
Attie, A., Pittman, R. C., & Steinberg, D. H. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.10.5923 · Cited by 51 · see citing works
Prakash, T. P., Kinberger, G. A., Murray, H. M., Chappell, A. E., Riney, S., Graham, M. J., Lima, W. F., Swayze, E. E., & Seth, P. P. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.04.063 · Cited by 51 · see citing works
Targeted In Vivo Delivery of siRNA and an Endosome-Releasing Agent to Hepatocytes
Sebestyén, M. G., Wong, S. C., Trubetskoy, V. S., et al. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1538-5_10 · Cited by 50 · see citing works
Solubilization of hepatic binding sites for asialo-glycoproteins
Morell, A. G., & Scheinberg, I. H. (1972) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(72)90679-1 · Cited by 38 · see citing works
SIMPSON, D. L., Cawley, D. B., & Herschman, H. R. (1982) · Cell · doi:10.1016/0092-8674(82)90163-5 · Cited by 38 · see citing works
Kolb-Bachofen, V. (1981) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(81)90200-5 · Cited by 30 · see citing works
Synthesis of some cluster galactosides and their effect on the hepatic galactose-binding system
Kawaguchi, K., Kuhlenschmidt, M. S., Roseman, S., & Lee, Y. C. (1980) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(80)90121-6 · Cited by 29 · see citing works
Targeting of antiviral drugs by coupling with protein carriers
FIUME, L., Busi, C., & Mattioli, A. (1983) · FEBS Letters · doi:10.1016/0014-5793(83)80108-2 · Cited by 21 · see citing works
Novel therapies for severe dyslipidemia originating from human genetics
Gaudet, D. (2016) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000281 · Cited by 18 · see citing works
Wooddell, C. I., Zhu, R., Hamilton, H. L., et al. (2018) · Journal of Hepatology · doi:10.1016/s0168-8278(18)30255-1 · Cited by 15 · see citing works
Rohlff, C., Watson, S. A., Morris, T. M., et al. (1999) · PubMed · Cited by 13 · see citing works
Gilbert Ashwell: sweet on science
(2008) · Nature Medicine · doi:10.1038/nm0608-608 · Cited by 13 · see citing works
Migawa, M. T., Prakash, T. P., Vasquez, G., et al. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.03.070 · Cited by 9 · see citing works
NEW CLASS OF DRUGS: THERAPEUTIC RNAi INHIBITION OF PCSK9 AS A SPECIFIC LDL-C LOWERING THERAPY.
Strat, A. L., Ghiciuc, C. M., Lupușoru, C. E., et al. (2016) · The Medical-Surgical Journal · Cited by 9 · see citing works
Induction of RNAi Responses by Short Left-Handed Hairpin RNAi Triggers
Hagopian, J. C., Hamil, A. S., van den Berg, A., Meade, B. R., Eguchi, A., Palm‐Apergi, C., & Dowdy, S. F. (2017) · Nucleic Acid Therapeutics · doi:10.1089/nat.2017.0686 · Cited by 5 · see citing works
Self-citationCarney, E. F. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.123 · Cited by 3 · see citing works
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Research works printed but not linked: 1
- Alnylam. (2018). Alnylam presents new clinical results from the Apollo Phase 3 study of Patisiran at the 16th international symposium on amyloidosis, http://investors .alnylam.com/news-releases/news-release-details/alnylam- presents-new-clinical-results-apollo-phase-3-study Accessed on April 23, 2018.
Cited by
Sorted by citations
The evolution of commercial drug delivery technologies
Vargason, A. M., Anselmo, A. C., & Mitragotri, S. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00698-w · Cited by 1,361 · see citing works
Antisense technology: an overview and prospectus
Crooke, S. T., Baker, B. F., Crooke, R. M., & Liang, X.-H. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00162-z · Cited by 775 · 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
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
Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a)
Koren, M. J., Moriarty, P. M., Baum, S. J., Neutel, J., Hernandez-Illas, M., Weintraub, H. S., Florio, M., Kassahun, H., Melquist, S., Varrieur, T., et al. (2022) · Nature Medicine · doi:10.1038/s41591-021-01634-w · Cited by 239 · see citing works
Lipid-based nanoparticle formulations for small molecules and RNA drugs
Ickenstein, L. M., & Garidel, P. (2019) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2019.1669558 · Cited by 193 · see citing works
The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans
Borén, J., Packard, C. J., & Taskinen, M.-R. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00474 · Cited by 196 · see citing works
RNA delivery biomaterials for the treatment of genetic and rare diseases
Zhao, W., Hou, X., Vick, O. G., & Dong, Y. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119291 · Cited by 82 · see citing works
Inclisiran: a novel agent for lowering apolipoprotein B–containing lipoproteins
Warden, B. A., & Duell, P. B. (2021) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000001053 · Cited by 62 · see citing works
Ebenezer, O., Comoglio, P., Wong, G. K.-S., & Tuszynski, J. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24044019 · Cited by 39 · see citing works
Pandey, M., Ojha, D., Bansal, S., Rode, A. B., & Chawla, G. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.101003 · Cited by 23 · see citing works
Ballman, K. K., Peek, V. L., Sloan, J. H., Li, J., Konrad, R. J., & Wen, Y. (2024) · The AAPS Journal · doi:10.1208/s12248-024-00914-w · Cited by 4 · see citing works
Hu, J., Wang, J., Zhang, H., Jiang, Y., Deng, L., Long, E., & Liu, S. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1758366 · Cited by 3 · see citing works
Wu, A.-X., Wang, X.-J., Zhao, C., Hu, J.-Q., Li, J.-W., Xu, Y., Li, Y., & Liu, S. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108178 · Cited by 1 · see citing works
- Authors
- Springer, A. D., & Dowdy, S. F.
- Affiliations
- University of California San Diego (US)
- Venue
- Nucleic Acid Therapeutics
- Publisher
- SAGE Publications
- Published
- 2018-06
- Volume
- 28
- Issue
- 3
- Pages
- 109-118
- ISSN
- 2159-3337 (ISSN-L)
- 2159-3345
- PMC
- PMC5994659
- OpenAlex
- W2803566305
- Cited by
- 711
- References
- 103
- Citations by year
- 2026: 104 · 2025: 113 · 2024: 118 · 2023: 99 · 2022: 99 · 2021: 90 · 2020: 50 · 2019: 35 · 2018: 2
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nucleic Acid Therapeutics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (R21EY027507)
- 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 › RNA and protein synthesis mechanisms
- Keywords
- siRNA delivery, RNAi therapeutics, N-acetylgalactosamine, asialoglycoprotein receptor, hepatocyte targeting, endocytosis, endosomal escape, antisense oligonucleotides, clinical trials
- MeSH terms
- Acetylgalactosamine, Clinical Trials as Topic, Endocytosis, Glycoconjugates, Liver, Neoplasms, Parkinson Disease, Endosomes, Virus Diseases, Gene Transfer Techniques, Hepatocytes, RNA, Small Interfering, Asialoglycoprotein Receptor, Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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