Antisense oligonucleotides: translation from mouse models to human neurodegenerative diseases
Open accessAbstract
Multiple neurodegenerative diseases are characterized by single-protein dysfunction and aggregation. Treatment strategies for these diseases have often targeted downstream pathways to ameliorate consequences of protein dysfunction; however, targeting the source of that dysfunction, the affected protein itself, seems most judicious to achieve a highly effective therapeutic outcome. Antisense oligonucleotides (ASOs) are small sequences of DNA able to target RNA transcripts, resulting in reduced or modified protein expression. ASOs are ideal candidates for the treatment of neurodegenerative diseases, given numerous advancements made to their chemical modifications and delivery methods. Successes achieved in both animal models and human clinical trials have proven ASOs both safe and effective. With proper considerations in mind regarding the human applicability of ASOs, we anticipate ongoing in vivo research and clinical trial development of ASOs for the treatment of neurodegenerative diseases.
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ASOs possess modularity-they can be designed to modulate splicing, degrade mRNA, or inhibit miRNAs.
“One advantage ASOs do possess over siRNA is their modularity—they can be designed to modulate splicing, degrade mRNA, or even inhibit miRNAs”
From Elucidating brain transport pathways and cell type-dependent gene silencing of a durable lipid–siRNA conjugate administered into cerebrospinal fluid (2025) · cites this paper as [56]
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Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · cited 1× · see citing works
“It is well established that the apolipoprotein isoform ApoE-ε4 confers a 2- to 12-fold risk for developing AD in humans, depending on the number of ε4 alleles (Corder et al., 1993).”
Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062 · cited 2× · see citing works
“OncemutantHtt is translated, the expanded polyglutamine (polyQ) protein likely mediates a toxic gain of function through the formation of intraneuronal aggregates or interaction with other proteins (Ordway et al., 1997; Rubinsztein, 2002).”
Origins and Mechanisms of miRNAs and siRNAs
Carthew, R. W., & Sontheimer, E. J. (2009) · Cell · doi:10.1016/j.cell.2009.01.035 · Cited by 5,023 · cited 8× · see citing works
“Such a strategy might be most beneficial for disorders with a known splicing defect to either restore protein function or to exclude mutated stretches of DNA.”
InfluentialDeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.011 · Cited by 4,936 · see citing works
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Sevigny, J., Chiao, P., Bussière, T., Weinreb, P. H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., et al. (2016) · Nature · doi:10.1038/nature19323 · Cited by 3,059 · cited 1× · see citing works
“Antibodies targeted against Ab, solanezumab, and aducanumab are currently in clinical trial and reporting efficacy (Sevigny et al., 2016; Siemers et al., 2016), suggesting antibody-mediated therapeutics are on par with ASOs in their clinical application.”
Luk, K. C., Kehm, V., Carroll, J., Zhang, B., O’Brien, P., Trojanowski, J. Q., & Lee, V. M.-Y. (2012) · Science · doi:10.1126/science.1227157 · Cited by 2,563 · cited 2× · see citing works
“, 2006), and alpha-synuclein (Luk et al., 2012; Mougenot et al., 2012), as the drivers of pathological propagation within the brain.”
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · cited 1× · see citing works
“Both 20-O-methyl and 20-O-methoxyethyl modifications are commonly used in preclinical research and clinical trials. common in particular base sequences) are potent immune activators (Younis et al., 2006) and, therefore, are often avoided in designing ASOs for in vivo application.”
Treatment of HCV Infection by Targeting MicroRNA
Janssen, H. L. A., Reesink, H. W., Lawitz, E., Zeuzem, S., Rodriguez‐Torres, M., Patel, K., van der Meer, A. J., Patick, A. K., Chen, A. P., Zhou, Y., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1209026 · Cited by 2,206 · cited 1× · see citing works
“This strategy is already being applied successfully in clinical trials for hepatitis C infection (Janssen et al., 2013).”
Tau Suppression in a Neurodegenerative Mouse Model Improves Memory Function
SantaCruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., et al. (2005) · Science · doi:10.1126/science.1113694 · Cited by 2,014 · see citing works
Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892 · cited 1× · see citing works
“Since its identification in 1993 as a contributing factor to fALS (Rosen et al., 1993), SOD1 has become an important target for disease intervention.”
Dendritic Function of Tau Mediates Amyloid-β Toxicity in Alzheimer's Disease Mouse Models
Ittner, L. M., Ke, Y. D., Delerue, F., Bi, M., Gladbach, A., van Eersel, J., Wölfing, H., Chieng, B. C., Christie, M. J., Napier, I. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.036 · Cited by 1,821 · see citing works
Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis
Ling, S.-C., Polymenidou, M., & Cleveland, D. W. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.033 · Cited by 1,811 · see citing works
Transmission and spreading of tauopathy in transgenic mouse brain
Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1901 · Cited by 1,803 · cited 1× · see citing works
“It is well established that the apolipoprotein isoform ApoE-ε4 confers a 2- to 12-fold risk for developing AD in humans, depending on the number of ε4 alleles (Corder et al., 1993).”
Propagation of Tau Pathology in a Model of Early Alzheimer's Disease
de Calignon, A., Polydoro, M., Suárez-Calvet, M., William, C., Adamowicz, D. H., Kopeikina, K. J., Pitstick, R., Sahara, N., Ashe, K. H., Carlson, G. A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.033 · Cited by 1,427 · cited 1× · see citing works
“Cumulative evidence points to extracellular proteins, including tau (Clavaguera et al., 2009; de Calignon et al., 2012; Holmes and Diamond, 2014), amyloid beta (Eisele et al., 2010; Meyer-Luehmann et al., 2006), and alpha-synuclein (Luk et al., 2012; Mougenot et al., 2012), as the drivers of…”
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 · cited 7× · see citing works
“ASOs consisting of fully modified 20 sugar moieties do not enable RNase H enzyme activity but instead support non-degrading ASO mechanisms, such as changes to alternative splicing or translational inhibition (Bennett and Swayze, 2010).”
InfluentialMajounie, E., Renton, A. E., Mok, K., Dopper, E. G., Waite, A., Rollinson, S., Chiò, A., Restagno, G., Nicolaou, N., Simon-Sanchez, J., et al. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70043-1 · Cited by 1,210 · see citing works
Molecular biology of amyotrophic lateral sclerosis: insights from genetics
Pasinelli, P., & Brown, R. H. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1971 · Cited by 1,107 · cited 1× · see citing works
“An overwhelming 90% of ALS cases have no known cause, termed sporadic or singleton ALS (sALS), whereas 10% of cases comprise familial ALS (fALS) and arise from gene mutations (Pasinelli and Brown, 2006).”
Exogenous Induction of Cerebral ß-Amyloidogenesis Is Governed by Agent and Host
Meyer-Luehmann, M., Coomaraswamy, J., Bolmont, T., Kaeser, S., Schaefer, C., Kilger, E., Neuenschwander, A., Abramowski, D., Frey, P., Jaton, A. L., et al. (2006) · Science · doi:10.1126/science.1131864 · Cited by 971 · cited 4× · see citing works
“, 2012; Holmes and Diamond, 2014), amyloid beta (Eisele et al., 2010; Meyer-Luehmann et al., 2006), and alpha-synuclein (Luk et al.”
InfluentialMorris, M., Maeda, S., Vossel, K., & Mucke, L. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.009 · Cited by 899 · cited 1× · see citing works
“Under normal conditions, tau functions to stabilize microtubules and may also be involved in intracellular signaling, scaffolding, and neurogenesis (Morris et al., 2011).”
RNA Toxicity from the ALS/FTD C9ORF72 Expansion Is Mitigated by Antisense Intervention
Donnelly, C. J., Zhang, P.-W., Pham, J. T., Haeusler, A. R., Mistry, N. A., Vidensky, S., Daley, E. L., Poth, E. M., Hoover, B., Fines, D. M., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.015 · Cited by 877 · see citing works
Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides
Geary, R. S., Norris, D. A., Yu, R. Z., & Bennett, C. F. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.01.008 · Cited by 846 · see citing works
Ribonuclease H: the enzymes in eukaryotes
Cerritelli, S. M., & Crouch, R. J. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.06908.x · Cited by 816 · see citing works
Kordasiewicz, H. B., Stanek, L. M., Wancewicz, E. V., Mazur, C., McAlonis, M. M., Pytel, K. A., Artates, J. W., Weiss, A., Cheng, S. H., Shihabuddin, L. S., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.05.009 · Cited by 770 · cited 14× · see citing works
“Amajor breakthrough for an ASO therapy for HD reported on the in vivo effectiveness of ASOs targeted against mutant Htt mRNA by employing several mouse models of HD as well as testing intrathecal infusion in non-human primates (Kordasiewicz et al., 2012).”
InfluentialHua, Y., Sahashi, K., Rigo, F., Hung, G., Horev, G., Bennett, C. F., & Krainer, A. R. (2011) · Nature · doi:10.1038/nature10485 · Cited by 744 · cited 1× · see citing works
“Peripheral administration of ASO surprisingly provided substantial phenotypic rescue and significantly prolonged survival (Hua et al., 2011), suggesting a peripheral component of SMA is very important in mouse models.”
MicroRNA-206 Delays ALS Progression and Promotes Regeneration of Neuromuscular Synapses in Mice
Williams, A. H., Valdez, G., Moresi, V., Qi, X., McAnally, J., Elliott, J. L., Bassel‐Duby, R., Sanes, J. R., & Olson, E. N. (2009) · Science · doi:10.1126/science.1181046 · Cited by 738 · see citing works
Sareen, D., O’Rourke, J. G., Meera, P., Muhammad, A. K. M. G., Grant, S., Simpkinson, M., Bell, S., Carmona, S., Ornelas, L., Sahabian, A., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3007529 · Cited by 670 · cited 6× · see citing works
“, 2013), restored normal gene expression markers (Donnelly et al., 2013; Lagier-Tourenne et al., 2013; Sareen et al., 2013), and protected against glutamate toxicity (Donnelly et al.”
InfluentialAntisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse modelPreprint
Hua, Y., Sahashi, K., Hung, G., Rigo, F., Passini, M. A., Bennett, C. F., & Krainer, A. R. (2010) · Genes & Development · doi:10.1101/gad.1941310 · Cited by 665 · cited 3× · see citing works
“In an effort to achieve central delivery, ASO 10-27 was infused directly into the lateral ventricle of hSMN2 mice, resulting in dose-dependent, long-lasting exon 7 inclusion and increased total SMN protein within the spinal cord (Hua et al., 2010).”
Miller, T. M., Pestronk, A., David, W., Rothstein, J., Simpson, E., Appel, S. H., Andres, P. L., Mahoney, K., Allred, P., Alexander, K., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70061-9 · Cited by 617 · cited 4× · see citing works
“This first-in-man study for intrathecal administration of the ASO demonstrated an excellent safety profile and established important pharmacokinetic measurements (Miller et al., 2013).”
InfluentialSelf-citationResults from a phase 1 study of nusinersen (ISIS-SMN Rx ) in children with spinal muscular atrophy
Chiriboga, C. A., Swoboda, K. J., Darras, B. T., Iannaccone, S. T., Montes, J., Vivo, D. C. D., Norris, D. A., Bennett, C. F., & Bishop, K. M. (2016) · Neurology · doi:10.1212/wnl.0000000000002445 · Cited by 613 · see citing works
Bace1 modulates myelination in the central and peripheral nervous system
Hu, X., Hicks, C. W., He, W., Wong, P., Macklin, W. B., Trapp, B. D., & Yan, R. (2006) · Nature Neuroscience · doi:10.1038/nn1797 · Cited by 608 · cited 1× · see citing works
“Whereas exciting from a treatment perspective, BACE reduction by ASO may carry several downsides associated with altering normal BACE function, as several groups have reported negative phenotypes in BACE-null mice (Dominguez et al., 2005; Hu et al., 2006; Laird et al., 2005).”
Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export
Lei, P., Ayton, S., Finkelstein, D. I., Spoerri, L., Ciccotosto, G. D., Wright, D. K., Wong, B. X. W., Adlard, P. A., Cherny, R. A., Lam, L. Q., et al. (2012) · Nature Medicine · doi:10.1038/nm.2613 · Cited by 594 · see citing works
Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists
Vollmer, J., & Krieg, A. Μ. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2008.12.008 · Cited by 584 · cited 3× · see citing works
“An exception might be when immune stimulation is a desired property, for example with immunotherapies (Vollmer and Krieg, 2009).”
Dragatsis, I., Levine, M. S., & Zeitlin, S. O. (2000) · Nature Genetics · doi:10.1038/81593 · Cited by 580 · cited 1× · see citing works
“Huntingtin has known physiological roles in neuronal survival (Rigamonti et al., 2000) and axon stability (Dragatsis et al., 2000).”
Yanamandra, K., Kfoury, N., Jiang, H., Mahan, T. E., Ma, S., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.046 · Cited by 574 · cited 2× · see citing works
“PS19 mice, expressing the P301SMAPTmutation, exhibit widespread phosphorylated tau, neuronal loss, and premature death (Yoshiyama et al., 2007).”
Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice
Becker, L. A., Huang, B., Bieri, G., Ma, R., Knowles, D. A., Jafar-Nejad, P., Messing, J., Kim, H. J., Soriano, A., Auburger, G., et al. (2017) · Nature · doi:10.1038/nature22038 · Cited by 571 · see citing works
Hua, Y., Vickers, T. A., Okunola, H. L., Bennett, C. F., & Krainer, A. R. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.01.014 · Cited by 570 · cited 2× · see citing works
“Independent validation of the critical role of ISS-N1 in exon 7 skipping and intervention using ASOs was executed using an ASO ‘‘microwalk’’ along SMN2, identifying 20-MOE ASOs that block heterogeneous nuclear ribonucleoprotein (hnRNP) A1/A2 motifs within the ISS-N1 sequence (Hua et al., 2008).”
Peripherally Applied Aβ-Containing Inoculates Induce Cerebral β-Amyloidosis
Eisele, Y. S., Obermüller, U., Heilbronner, G., Baumann, F., Kaeser, S. A., Wolburg, H., Walker, L. C., Staufenbiel, M., Heikenwalder, M., & Jucker, M. (2010) · Science · doi:10.1126/science.1194516 · Cited by 568 · cited 1× · see citing works
“…points to extracellular proteins, including tau (Clavaguera et al., 2009; de Calignon et al., 2012; Holmes and Diamond, 2014), amyloid beta (Eisele et al., 2010; Meyer-Luehmann et al., 2006), and alpha-synuclein (Luk et al., 2012; Mougenot et al., 2012), as the drivers of pathological…”
Lagier‐Tourenne, C., Baughn, M. W., Rigo, F., Sun, S., Liu, P., Li, H., Jiang, J., Watt, A. T., Chun, S. J., Katz, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318835110 · Cited by 555 · cited 1× · see citing works
“Whereas exciting from a treatment perspective, BACE reduction by ASO may carry several downsides associated with altering normal BACE function, as several groups have reported negative phenotypes in BACE-null mice (Dominguez et al., 2005; Hu et al., 2006; Laird et al., 2005).”
<i>C9orf72</i> is required for proper macrophage and microglial function in mice
O’Rourke, J. G., Bogdanik, L., Yáñez, A., Lall, D., Wolf, A. J., Muhammad, A. K. M. G., Ho, R., Carmona, S., Vit, J. P., Zarrow, J., et al. (2016) · Science · doi:10.1126/science.aaf1064 · Cited by 550 · cited 1× · see citing works
“OncemutantHtt is translated, the expanded polyglutamine (polyQ) protein likely mediates a toxic gain of function through the formation of intraneuronal aggregates or interaction with other proteins (Ordway et al., 1997; Rubinsztein, 2002).”
Self-citationPassini, M. A., Bu, J., Richards, A. M., Kinnecom, C., Sardi, S. P., Stanek, L. M., Hua, Y., Rigo, F., Matson, J. E., Hung, G., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3001777 · Cited by 547 · cited 1× · see citing works
“…acetylcholine (Gotkine et al., 2013), phospholipase A2a (Solomonov et al., 2016), p75 (Turner et al., 2003), and prostate apoptosis response 4 (Pedersen et al., 2000) as potential targets for ASOs tomitigate ALS, and putative targets like ataxin-2 have been proposed for future research (van…”
Splice-switching antisense oligonucleotides as therapeutic drugs
Havens, M. A., & Hastings, M. L. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw533 · Cited by 541 · see citing works
Jiang, J., Zhu, Q., Gendron, T. F., Saberi, S., McAlonis-Downes, M., Seelman, A., Stauffer, J. E., Jafar-nejad, P., Drenner, K., Schulte, D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.006 · Cited by 536 · cited 8× · see citing works
“…of C9orf72 from birth in mice does show abnormalities (Jiang et al., 2016; O’Rourke et al., 2016), raising some concerns for an ASO-mediated lowering strategy, the short-term administration of ASO to the endogenous mouse homolog was well tolerated (Jiang et al., 2016; Lagier-Tourenne et al., 2013).”
InfluentialEvidence for natural antisense transcript-mediated inhibition of microRNA function
Faghihi, M., Zhang, M., Huang, J., Modarresi, F., van der Brug, M. P., Nalls, M., Cookson, M., Laurent, G. S. S., & Wahlestedt, C. (2010) · Genome Biology · doi:10.1186/gb-2010-11-5-r56 · Cited by 525 · cited 1× · see citing works
“Several regulatory miRNAs, including miR-34a and miR-206, were found to be highly expressed in mouse models of AD or postmortem human AD brain tissues (Faghihi et al., 2010; Lee et al., 2012; Wang et al., 2009).”
Laird, F. M., Cai, H., Savonenko, A. V., Farah, M. H., He, K., Melnikova, T., Wen, H., Chiang, H.-C., Xu, G., Koliatsos, V. E., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2766-05.2005 · Cited by 521 · cited 1× · see citing works
“Whereas exciting from a treatment perspective, BACE reduction by ASO may carry several downsides associated with altering normal BACE function, as several groups have reported negative phenotypes in BACE-null mice (Dominguez et al., 2005; Hu et al., 2006; Laird et al., 2005).”
DeVos, S. L., Miller, R. L., Schoch, K. M., Holmes, B. B., Kebodeaux, C. S., Wegener, A. J., Chen, G., Shen, T., Tran, H., Nichols, B., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aag0481 · Cited by 516 · see citing works
Self-citationAntisense oligonucleotide therapy for neurodegenerative disease
Smith, R. A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25424 · Cited by 506 · cited 7× · see citing works
“…in mice (DeVos et al., 2013; Kordasiewicz et al., 2012; Lagier-Tourenne et al., 2013; Passini et al., 2011), rats (Smith et al., 2006), and non-human primates (Kordasiewicz et al., 2012; Passini et al., 2011; Rigo et al., 2014; Smith et al., 2006) using intraventricular or intrathecal injection.”
InfluentialSwayze, E. E., Siwkowski, A. M., Wancewicz, E. V., Migawa, M. T., Wyrzykiewicz, T. K., Hung, G., Monia, B. P., & Bennett, A. C. F. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl1071 · Cited by 473 · see citing works
CNS Drug Design Based on Principles of Blood‐Brain Barrier Transport
Pardridge, W. M. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70051781.x · Cited by 460 · cited 1× · see citing works
“An overwhelming 90% of ALS cases have no known cause, termed sporadic or singleton ALS (sALS), whereas 10% of cases comprise familial ALS (fALS) and arise from gene mutations (Pasinelli and Brown, 2006).”
Singh, N. K., Singh, N. N., Androphy, E. J., & Singh, R. N. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.4.1333-1346.2006 · Cited by 452 · cited 1× · see citing works
“…Htt allele, specificity for the mutant allele was confirmed with specific reduction of mutant Htt without change to the normal mRNA or protein (Southwell et al., 2015) and demonstrated an extended duration of action from 16 to 32 weeks depending on the 20 modification (Skotte et al., 2014).”
Improved targeting of miRNA with antisense oligonucleotides
Davis, S. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl183 · Cited by 422 · cited 1× · see citing works
“ASOs act by binding thesemicroRNA (miRNA) targets to inhibit their mRNA interaction by sequestration or degradation (Davis et al., 2006, 2009).”
BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease
Vassar, R. J. (2014) · Alzheimer s Research & Therapy · doi:10.1186/s13195-014-0089-7 · Cited by 413 · cited 1× · see citing works
“Pharmacological b-secretase (BACE) inhibitors have achieved preclinical success (Vassar, 2014) and have advanced into phase II/III clinical trials (NCT02245737 and NCT02783573; https:// clinicaltrials.gov).”
Wild-Type Huntingtin Protects from Apoptosis Upstream of Caspase-3
Rigamonti, D., Bauer, J. H., De‐Fraja, C., Conti, L., Sipione, S., Sciorati, C., Clementi, E., Hackam, A. S., Hayden, M. R., Li, Y., et al. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-10-03705.2000 · Cited by 406 · see citing works
Prion-like acceleration of a synucleinopathy in a transgenic mouse model
Mougenot, A.-L. J., Nicot, S., Bencsik, A. A., Morignat, E., Verchère, J., Lakhdar, L., Legastelois, S., & Baron, T. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.06.022 · Cited by 375 · cited 2× · see citing works
“, 2006), and alpha-synuclein (Luk et al., 2012; Mougenot et al., 2012), as the drivers of pathological propagation within the brain.”
Phase 3 solanezumab trials: Secondary outcomes in mild Alzheimer's disease patients
Siemers, E. R., Sundell, K. L., Carlson, C., Case, M., Sethuraman, G., Liu‐Seifert, H., Dowsett, S. A., Pontecorvo, M. J., Dean, R. A., & Demattos, R. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.06.1893 · Cited by 370 · see citing works
Ordway, J. M., Tallaksen‐Greene, S. J., Gutekunst, C., Bernstein, E. M., Cearley, J. A., Wiener, H. W., Dure, L. S., Lindsey, R., Hersch, S. M., Jope, R. S., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80464-x · Cited by 370 · cited 1× · see citing works
“Subsequently, morpholino ASOs were found to elevate SMN protein expression, drastically extend lifespan, and improve neuromuscular junction structure in two separate mouse models of varying SMA severity (Osman et al., 2014).”
C9orf72 BAC Mouse Model with Motor Deficits and Neurodegenerative Features of ALS/FTD
Liu, Y., Pattamatta, A., Zu, T., Reid, T. S., Bardhi, O., Borchelt, D., Yachnis, A. T., & Ranum, L. P. W. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.005 · Cited by 368 · cited 2× · see citing works
“The recent development of animal models that express the abnormally expanded C9orf72 gene aims to bridge the gap between ASO application in iPSC-derived cells and diseasemodels (Jiang et al., 2016; Liu et al., 2016; O’Rourke et al., 2016; Peters et al., 2015).”
Phenotypic and Biochemical Analyses of BACE1- and BACE2-deficient Mice
Dominguez, D. I., Tournoy, J., Hartmann, D., Huth, T., Cryns, K., Deforce, S., Serneels, L., Espuny-Camacho, I., Marjaux, E., Craessaerts, K., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505249200 · Cited by 359 · cited 1× · see citing works
“Whereas exciting from a treatment perspective, BACE reduction by ASO may carry several downsides associated with altering normal BACE function, as several groups have reported negative phenotypes in BACE-null mice (Dominguez et al., 2005; Hu et al., 2006; Laird et al., 2005).”
Butovsky, O., Jedrychowski, M. P., Cialic, R., Krasemann, S., Murugaiyan, G., Fanek, Z., Greco, D. J., Wu, P. M., Doykan, C. E., Kiner, O., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24304 · Cited by 358 · cited 2× · see citing works
“Intraventricular delivery of ASOs against miR-155, a target miRNA found to be upregulated in ALS tissues, resulted in de-repression of miR-155 targets throughout the brain and spinal cord and remarkably led to a significant extension in survival of SOD1 mutant mice (Butovsky et al., 2015; Koval et al., 2013).”
Determination of the Role of the Human RNase H1 in the Pharmacology of DNA-like Antisense Drugs
Wu, H., Lima, W. F., Zhang, H., Fan, A., Sun, H., & Crooke, S. T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311683200 · Cited by 351 · cited 1× · see citing works
“Degradation of the mRNA target via this mechanism begins in the nucleus, where the DNA-RNA pairing of ASOs to their mRNA target triggers recruitment of the enzyme RNase H1 (Wu et al., 2004).”
Control of alternative splicing through siRNA-mediated transcriptional gene silencing
Alló, M., Buggiano, V., Fededa, J. P., Petrillo, E., Schor, I., de la Mata, M., Agirre, E., Plass, M., Eyras, E., Elela, S. A., et al. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1620 · Cited by 340 · cited 1× · see citing works
“Similar to themechanisms by which ASOs act, RNAi enables gene expression changes, such as mRNA degradation, alternative splicing manipulation, miRNA inhibition, and transcriptional silencing (Alló et al., 2009; Carthew and Sontheimer, 2009).”
Butterfield, D. A., & Poon, H. F. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.05.007 · Cited by 328 · cited 1× · see citing works
“In addition, the behavioral changes observed in SAMP8 mice may be confounded by the naturally occurring neuropathological and behavioral phenotype likely resulting from age-related changes in numerous genes and proteins (Butterfield and Poon, 2005).”
Antisense oligonucleotide therapy for spinocerebellar ataxia type 2
Scoles, D. R., Meera, P., Schneider, M. D., Paul, S., Dansithong, W., Figueroa, K. P., Hung, G., Rigo, F., Bennett, C. F., Otis, T. S., et al. (2017) · Nature · doi:10.1038/nature22044 · Cited by 319 · cited 1× · see citing works
“ASO-mediated ATNX2 reduction in two separate SCA mouse models improvedmotor performance, corrected abnormal gene expression, and restored normal Purkinje cell electrophysiology (Scoles et al., 2017).”
Antisense Reduction of Tau in Adult Mice Protects against Seizures
DeVos, S. L., Goncharoff, D. K., Chen, G., Kebodeaux, C. S., Yamada, K., Stewart, F. R., Schuler, D. R., Maloney, S. E., Wozniak, D. F., Rigo, F., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2107-13.2013 · Cited by 311 · see citing works
Self-citationMocanu, M.-M., Nissen, A., Eckermann, K., Khlistunova, I., Biernat, J., Drexler, D., Petrova, O., Schönig, K., Bujard, H., Mandelkow, E., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2824-07.2008 · Cited by 297 · cited 2× · see citing works
“might be expected in light of previous findings in which doxycycline-induced tau transgene suppression could halt tau aggregates (Mocanu et al., 2008; Polydoro et al., 2013) and arrest”
Rodent Models of Amyotrophic Lateral Sclerosis
Philips, T., & Rothstein, J. D. (2015) · Current Protocols in Pharmacology · doi:10.1002/0471141755.ph0567s69 · Cited by 292 · cited 1× · see citing works
“Mouse data demonstrate that expression of mutant SOD1 causes motor neuron disease whereas genetic deletion of SOD1 does not (Philips and Rothstein, 2015).”
Pharmacokinetic Properties of 2′-O-(2-Methoxyethyl)-Modified Oligonucleotide Analogs in Rats
Geary, R. S., Watanabe, T. A., Truong, L., Freier, S., Lesnik, E. A., Sioufi, N. B., Sasmor, H. M., Manoharan, M., & Levin, A. A. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38831-7 · Cited by 289 · cited 1× · see citing works
“A major disadvantage to the PS backbone modification is the potential inflammatory response generated at high concentrations (Crooke, 2007) and prohibitive affinity for plasma protein binding (Geary et al., 2001), which may produce adverse effects and other limitations in a clinical setting.”
Rigo, F., Chun, S. J., Norris, D. A., Hung, G., Lee, S., Matson, J., Fey, R. A., Gaus, H., Hua, Y., Grundy, J. S., et al. (2014) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.212407 · Cited by 283 · see citing works
Lessons from animal models of Huntington's disease
Rubinsztein, D. C. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(01)02625-7 · Cited by 281 · cited 2× · see citing works
“OncemutantHtt is translated, the expanded polyglutamine (polyQ) protein likely mediates a toxic gain of function through the formation of intraneuronal aggregates or interaction with other proteins (Ordway et al., 1997; Rubinsztein, 2002).”
miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model
Lee, S., Chu, K., Jung, K., Kim, J. H., Huh, J., Yoon, H., Park, D., Lim, J., Kim, J., Jeon, D., et al. (2012) · Annals of Neurology · doi:10.1002/ana.23588 · Cited by 275 · cited 3× · see citing works
“Similar results were seen with intranasal delivery (Lee et al., 2012), highlighting this method as a possible noninvasive delivery route for ASOs.”
Peters, O. M., Cabrera, G. T., Tran, H., Gendron, T. F., McKeon, J. E., Metterville, J., Weiss, A., Wightman, N., Salameh, J. S., Kim, J., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.11.018 · Cited by 259 · see citing works
Selective inhibition of mutant Ha-ras mRNA expression by antisense oligonucleotides.
Monia, B. P., Johnston, J. F., Ecker, D. J., Zounes, M. A., Lima, W. F., & Freier, S. M. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)88650-7 · Cited by 254 · see citing works
A single administration of morpholino antisense oligomer rescues spinal muscular atrophy in mouse
Porensky, P. N., Mitrpant, C., McGovern, V. L., Bevan, A. K., Foust, K. D., Kaspar, B. K., Wilton, S. D., & Burghes, A. H. M. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr600 · Cited by 248 · cited 2× · see citing works
“Using a morpholino design, researchers identified a 3-fold increase in exon 7 inclusion and SMN protein expression within the brain and spinal cord after a single ICV injection in SMA model mice, conferring a dose-dependent, 97-day extension in survival (Porensky et al., 2012).”
Holth, J. K., Bomben, V. C., Reed, J. G., Inoue, T., Younkin, L., Younkin, S. G., Pautler, R. G., Botas, J., & Noebels, J. L. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3191-12.2013 · Cited by 238 · cited 1× · see citing works
“In addition to dementia, emerging evidence suggests tau may also mediate hyperexcitability in neurodegenerative states (Holth et al., 2013; Ittner et al., 2010; Roberson et al., 2007).”
Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice
Koval, E. D., Shaner, C., Zhang, P., du Maine, X., Fischer, K., Tay, J., Chau, B. N., Wu, G. F., & Miller, T. M. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt261 · Cited by 236 · see citing works
Self-citationPrion-like Properties of Tau Protein: The Importance of Extracellular Tau as a Therapeutic Target
Holmes, B. B., & Diamond, M. I. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.r114.549295 · Cited by 202 · see citing works
Potent inhibition of microRNA in vivo without degradation
Davis, S. P., Propp, S. S., Freier, S. M., Jones, L., Serra, M. J., Kinberger, G. A., Bhat, B., Swayze, E. E., Bennett, C. F., & Esau, C. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn904 · Cited by 201 · see citing works
Kumar, V. B., Farr, S. A., Flood, J. F., Kamlesh, V., Franko, M. W., Banks, W. A., & Morley, J. E. (2000) · Peptides · doi:10.1016/s0196-9781(00)00339-9 · Cited by 193 · cited 6× · see citing works
“…of C9orf72 from birth in mice does show abnormalities (Jiang et al., 2016; O’Rourke et al., 2016), raising some concerns for an ASO-mediated lowering strategy, the short-term administration of ASO to the endogenous mouse homolog was well tolerated (Jiang et al., 2016; Lagier-Tourenne et al., 2013).”
Influential(2007) · CRC Press eBooks · doi:10.1201/9780849387951 · Cited by 181 · cited 2× · see citing works
“A major disadvantage to the PS backbone modification is the potential inflammatory response generated at high concentrations (Crooke, 2007) and prohibitive affinity for plasma protein binding (Geary et al., 2001), which may produce adverse effects and other limitations in a clinical setting.”
Increased 4R-Tau Induces Pathological Changes in a Human-Tau Mouse Model
Schoch, K. M., DeVos, S. L., Miller, R. L., Chun, S. J., Norrbom, M., Wozniak, D. F., Dawson, H. N., Bennett, C. F., Rigo, F., & Miller, T. M. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.042 · Cited by 175 · cited 3× · see citing works
“In two human tau-expressing mouse models, ASO treatment significantly shifted splicing patterns to lower 4R tau without change to total tau levels (Schoch et al., 2016).”
InfluentialSelf-citationCurrent perspectives on intrathecal drug delivery
Christo, P. J., & Bottros, M. M. (2014) · Journal of Pain Research · doi:10.2147/jpr.s37591 · Cited by 174 · cited 12× · see citing works
“This pivotal study confirmed ASOs as an effective technique to target CNS proteins in vivo.”
InfluentialFirst "Antisense" Drug Will Treat CMV Retinitis
Marwick, C. (1998) · JAMA · doi:10.1001/jama.280.10.871-jmn0909-6-1 · Cited by 167 · see citing works
Østergaard, M. E., Southwell, A. L., Kordasiewicz, H. B., Watt, A. T., Skotte, N. H., Doty, C. N., Vaid, K., Villanueva, E. B., Swayze, E. E., Bennett, C. F., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt725 · Cited by 163 · cited 2× · see citing works
“This ASO and others have undergone further development and improvement for human application to increase the specificity of the ASO to >100fold for mutant Htt allele over normal allele (Østergaard et al., 2013).”
Chemically Modified Oligonucleotides Exhibit Decreased Immune Stimulation in Mice
Henry, S. P., Stecker, K., Brooks, D., Monteith, D., Conklin, B., & Bennett, C. F. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35315-7 · Cited by 152 · cited 1× · see citing works
“Both 20-O-Me and 20-MOE design are reported to have a lowered pro-inflammatory response and be well tolerated compared to unmodified motifs (Henry et al., 2000; Tluk et al., 2009).”
Bayever, E., Iversen, P. L., Bishop, M. R., Sharp, J. G., Tewary, H. K., Arneson, M. A., Pirruccello, S. J., Ruddon, R. W., Kessinger, A., Zon, G., et al. (1993) · Antisense Research and Development · doi:10.1089/ard.1993.3.383 · Cited by 149 · cited 1× · see citing works
“The first ASO to enter clinical trial, targeted against p53 in acute myelogenous leukemia, drew upon 20 years of chemical advancements prior to its introduction in 1993 (Bayever et al., 1993).”
A large animal model of spinal muscular atrophy and correction of phenotype
Duqué, S. I., Arnold, W. D., Odermatt, P., Li, X., Porensky, P. N., Schmelzer, L., Meyer, K., Kolb, S. J., Schümperli, D., Kaspar, B. K., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24332 · Cited by 136 · see citing works
d’Ydewalle, C. V. O., Ramos, D. M., Pyles, N. J., Ng, S., Gorz, M., Pilato, C. M., Ling, K., Kong, L., Ward, A. J., Rubin, L. L., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.11.033 · Cited by 136 · cited 1× · see citing works
“Other ASO targets, such as long non-coding RNA (lncRNA) SMN sequences, have also shown considerable promise inmodulating SMN expression and extending survival inmice (d’Ydewalle et al., 2017).”
Ma, Q., Zuo, X., Yang, F., Ubeda, O. J., Gant, D. J., Alaverdyan, M., Kiosea, N., Nazari, S., Chen, P. P., Nothias, F., et al. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3439-13.2014 · Cited by 135 · see citing works
Antisense and siRNA as agonists of Toll-like receptors
Agrawal, S., & Kandimalla, E. R. (2004) · Nature Biotechnology · doi:10.1038/nbt1042 · Cited by 131 · cited 1× · see citing works
“In vivo, the ASO is recognized as foreign DNA by toll-like receptors and likely causes ‘‘off-target’’ activation of the immune system (Agrawal and Kandimalla, 2004).”
Hinrich, A. J., Jodelka, F. M., Chang, J. L., Brutman, D., Bruno, A. M., Briggs, C. A., James, B. D., Stutzmann, G. E., Bennett, D. A., Miller, S. A., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201505846 · Cited by 127 · see citing works
Kamola, P. J., Kitson, J., Turner, G., Maratou, K., Eriksson, S., Panjwani, A. A., Warnock, L. C., Douillard‐Guilloux, G., Moores, K., Koppe, E. L., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv857 · Cited by 117 · cited 1× · see citing works
“For human clinical candidates, each ASO is screened in silico against the human genome and ‘‘hits’’ with one, two, or three mismatches are empirically tested for ASO-mediated changes of these mRNAs (Kamola et al., 2015; Monia et al., 1992).”
Skotte, N. H., Southwell, A. L., Østergaard, M. E., Carroll, J. B., Warby, S. C., Doty, C. N., Petoukhov, E., Vaid, K., Kordasiewicz, H. B., Watt, A. T., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107434 · Cited by 116 · cited 2× · see citing works
“…Htt allele, specificity for the mutant allele was confirmed with specific reduction of mutant Htt without change to the normal mRNA or protein (Southwell et al., 2015) and demonstrated an extended duration of action from 16 to 32 weeks depending on the 20 modification (Skotte et al., 2014).”
Baughan, T. D., Dickson, A. L., Osman, E. Y., & Lorson, C. L. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp076 · Cited by 115 · cited 1× · see citing works
“A single ICV injection of E1 bifunctional RNA into Smn / SMN2+/+ mice restored expression of SMN protein and improved weight gain (Baughan et al., 2009).”
Wild-type SOD1 overexpression accelerates disease onset of a G85R SOD1 mouse
Wang, L., Deng, H., Grisotti, G., Zhai, H., Siddique, T., & Roos, R. P. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp085 · Cited by 114 · see citing works
SOD1 in Cerebral Spinal Fluid as a Pharmacodynamic Marker for Antisense Oligonucleotide Therapy
Winer, L. K., Srinivasan, D., Chun, S. J., Lacomis, D., Jaffa, M., Fagan, A. M., Holtzman, D. M., Wancewicz, E. V., Bennett, C. F., Bowser, R. P., et al. (2012) · JAMA Neurology · doi:10.1001/jamaneurol.2013.593 · Cited by 112 · cited 2× · see citing works
“ASO to determine efficacy in this ongoing study and to help direct design of future clinical trials (Crisp et al., 2015; Winer et al., 2013).”
Self-citationSouthwell, A. L., Smith, S. E. P., Davis, T. R., Caron, N. S., Villanueva, E. B., Xie, Y., Collins, J. A., Ye, M. L., Sturrock, A., Leavitt, B. R., et al. (2015) · Scientific Reports · doi:10.1038/srep12166 · Cited by 109 · cited 3× · see citing works
“Pre-symptomatic and post-symptomatic ASO administration in an HD mouse model (YAC128) lessened disease phenotypes (Kordasiewicz et al., 2012; Stanek et al., 2013), and when applied to a more severe, quickly progressing HD mouse model (R6/2), ASO treatment afforded a significant extension in survival (Kordasiewicz et a…”
He, X., Cooley, K., Chung, C. H. Y., Dashti, N., & Tang, J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3993-06.2007 · Cited by 107 · cited 1× · see citing works
“…mediating AD pathogenesis is not fully understood, the receptor may modulate APP localization and processing, resulting in increased Ab production (Fuentealba et al., 2007; He et al., 2007), and its different splice variants confer its ligand binding and signaling function (Sun and Soutar, 1999).”
Pharmacokinetics and Tissue Distribution of a Peptide Nucleic Acid After Intravenous Administration
McMahon, B. M., Mays, D. C., Lipsky, J. J., Stewart, J. A., Fauq, A. H., & Richelson, E. (2002) · Antisense and Nucleic Acid Drug Development · doi:10.1089/108729002760070803 · Cited by 106 · cited 1× · see citing works
“Although thesemodifications are advantageous for their potency and nuclease-resistant properties, problems associated with toxicity or poor penetration continue to be explored (McMahon et al., 2002; Swayze et al., 2007).”
Turner, B. J., Cheah, I. K.-M., Macfarlane, K. J., Lopes, E. C., Petratos, S., Langford, S. J., & Cheema, S. S. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02053.x · Cited by 97 · see citing works
Lorenz, P. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.2.582 · Cited by 94 · cited 1× · see citing works
“Once inside cells, ASOs are able to travel between the cytosol and nucleus via proposed binding to cellular molecules (Lorenz et al., 2000).”
Pedersen, W. A., Luo, H., Kruman, I. I., Kasarskis, E. J., & Mattson, M. P. (2000) · The FASEB Journal · doi:10.1096/fasebj.14.7.913 · Cited by 81 · cited 2× · see citing works
“…acetylcholine (Gotkine et al., 2013), phospholipase A2a (Solomonov et al., 2016), p75 (Turner et al., 2003), and prostate apoptosis response 4 (Pedersen et al., 2000) as potential targets for ASOs tomitigate ALS, and putative targets like ataxin-2 have been proposed for future research (van…”
Farr, S. A., Erickson, M. A., Niehoff, M. L., Banks, W. A., & Morley, J. E. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131883 · Cited by 72 · cited 2× · see citing works
“Senescence-accelerated mouseprone (SAMP8) mice (Erickson et al., 2012; Kumar et al., 2000) and, later, Tg2576 (K670M/N671L Swedish APP mutation; Farr et al., 2014) were treated with peripheral injection of the ASO.”
Electrophysiological biomarkers in spinal muscular atrophy: proof of concept
Arnold, W. D., Porensky, P. N., McGovern, V. L., Iyer, C. C., Duqué, S. I., Li, X., Meyer, K., Schmelzer, L., Kaspar, B. K., Kolb, S. J., et al. (2013) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.23 · Cited by 71 · see citing works
The DcpS inhibitor RG3039 improves motor function in SMA mice
Meerbeke, J. P. V., Gibbs, R. M., Plasterer, H. L., Miao, W., Feng, Z., Lin, M.-Y., Rucki, A. A., Wee, C. D., Xia, B., Sharma, S., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt257 · Cited by 71 · cited 2× · see citing works
“…pharmaceutical inhibitors, viral SMN gene replacement, stem cells, and small molecules, are under current investigation (Duque et al., 2015; Van Meerbeke et al., 2013; Zanetta et al., 2014), the early success of ASOs in clinical studies will likely make this approach a benchmark to which…”
Fuentealba, R. A., Barría, M. I., Lee, J., Cam, J., Araya, C., Escudero, C. A., Inestrosa, N. C., Bronfman, F. C., Bu, G., & Marzolo, M.-P. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-14 · Cited by 70 · cited 2× · see citing works
“…mediating AD pathogenesis is not fully understood, the receptor may modulate APP localization and processing, resulting in increased Ab production (Fuentealba et al., 2007; He et al., 2007), and its different splice variants confer its ligand binding and signaling function (Sun and Soutar, 1999).”
Sud, R., Geller, E. T., & Schellenberg, G. D. (2014) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2014.30 · Cited by 69 · see citing works
Stanek, L. M., Yang, W., Angus, S., Sardi, P., Hayden, M. R., Hung, G., Bennett, C. F., Cheng, S. H., & Shihabuddin, L. S. (2013) · Journal of Huntington s Disease · doi:10.3233/jhd-130057 · Cited by 66 · cited 2× · see citing works
“In human mutant (E10+14) tau-expressing mice, use of a tautargeted ASO significantly reduced total tau mRNA and protein (Sud et al., 2014), confirming in vivo application.”
A Negatively Acting Bifunctional RNA Increases Survival Motor Neuron Both In Vitro and In Vivo
Dickson, A., Osman, E. Y., & Lorson, C. L. (2008) · Human Gene Therapy · doi:10.1089/hum.2008.067 · Cited by 64 · cited 2× · see citing works
“This same group identified a separate target within the exon 8 splice site of SMN involved in recruitment of the splicing silencer, hnRNPA1, to stimulate upstream exon 7 inclusion (Dickson et al., 2008).”
Bogdanik, L. P., Osborne, M. A., Davis, C., Martin, W., Austin, A., Rigo, F., Bennett, C. F., & Lutz, C. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1509758112 · Cited by 63 · see citing works
Osman, E. Y., Bolding, M., Robbins, K. L., Lombardi, A., Atkinson, A. K., Brehm, A. J., & Lorson, C. L. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu198 · Cited by 62 · cited 1× · see citing works
“Subsequently, morpholino ASOs were found to elevate SMN protein expression, drastically extend lifespan, and improve neuromuscular junction structure in two separate mouse models of varying SMA severity (Osman et al., 2014).”
In vivo kinetic approach reveals slow SOD1 turnover in the CNS
Crisp, M. J., Mawuenyega, K. G., Patterson, B. W., Reddy, N. C., Chott, R. C., Self, W. K., Weihl, C. C., Jockel, J., Varadhachary, A. S., Bucelli, R. C., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci80705 · Cited by 58 · cited 2× · see citing works
“ASO to determine efficacy in this ongoing study and to help direct design of future clinical trials (Crisp et al., 2015; Winer et al., 2013).”
Self-citationErickson, M. A., Niehoff, M. L., Farr, S. A., Morley, J. E., Dillman, L. A., Lynch, K. M., & Banks, W. A. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-111517 · Cited by 57 · cited 2× · see citing works
“Additional ASO designs, including morpholino (Sun et al., 2014) or those targeting Htt by splicing manipulation (Evers et al., 2014), may provide alternative strategies to reduce Htt toxicity without lowering total protein.”
Evers, M. M., Tran, H.-D., Zalachoras, I., Meijer, O. C., den Dunnen, J. T., van Ommen, G. B., Aartsma-Rus, A. M., & van Roon‐Mom, W. (2013) · Nucleic Acid Therapeutics · doi:10.1089/nat.2013.0452 · Cited by 57 · cited 1× · see citing works
“Additional ASO designs, including morpholino (Sun et al., 2014) or those targeting Htt by splicing manipulation (Evers et al., 2014), may provide alternative strategies to reduce Htt toxicity without lowering total protein.”
Polydoro, M., de Calignon, A., Suárez‐Calvet, M., Sanchez, L., Kay, K. R., Nicholls, S. B., Roe, A. D., Pitstick, R., Carlson, G. A., Gómez‐Isla, T., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0881-13.2013 · Cited by 46 · cited 2× · see citing works
“might be expected in light of previous findings in which doxycycline-induced tau transgene suppression could halt tau aggregates (Mocanu et al., 2008; Polydoro et al., 2013) and arrest”
The neuromuscular impact of symptomatic SMN restoration in a mouse model of spinal muscular atrophy
Arnold, W. D., McGovern, V. L., Sanchez, B., Li, J., Corlett, K. M., Kolb, S. J., Rutkove, S. B., & Burghes, A. H. M. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.12.014 · Cited by 46 · cited 1× · see citing works
“Restoration of SMA expression also corrected electrophysiological and motor unit dysfunction in delta7-SMA mutant mice (Arnold et al., 2014, 2016).”
Sun, X., & Soutar, A. K. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00394.x · Cited by 44 · see citing works
Taking a risk: a therapeutic focus on ataxin-2 in amyotrophic lateral sclerosis?
van den Heuvel, D. M. A., Harschnitz, O., van den Berg, L. H., & Pasterkamp, R. J. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.09.001 · Cited by 43 · see citing works
Chauhan, N. B., & Siegel, G. J. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.01.008 · Cited by 40 · cited 1× · see citing works
“…with complete loss of BACE expression, researchers targeted the BACE cleavage site within APP, demonstrating that weekly intraventricular ASO injections in Tg2576 mice increased levels of soluble APPa and lowered levels of acetylcholinesterase, a marker of Ab toxicity (Chauhan and Siegel, 2007).”
Sun, X., Marque, L. O., Cordner, Z. A., Pruitt, J. L., Bhat, M., Li, P. P., Kannan, G., Ladenheim, E. E., Moran, T. H., Margolis, R. L., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu349 · Cited by 37 · cited 2× · see citing works
“Additional ASO designs, including morpholino (Sun et al., 2014) or those targeting Htt by splicing manipulation (Evers et al., 2014), may provide alternative strategies to reduce Htt toxicity without lowering total protein.”
Tluk, S., Jurk, M., Forsbach, A., Weeratna, R. D., Samulowitz, U., KRIEG, A. M., Bauer, S., & Vollmer, J. (2009) · International Immunology · doi:10.1093/intimm/dxp030 · Cited by 36 · cited 1× · see citing works
“Both 20-O-Me and 20-MOE design are reported to have a lowered pro-inflammatory response and be well tolerated compared to unmodified motifs (Henry et al., 2000; Tluk et al., 2009).”
Pao, P. W., Wee, K. B., Yee, W. C., & Pramono, Z. A. D. (2013) · Molecular Therapy · doi:10.1038/mt.2013.276 · Cited by 29 · cited 2× · see citing works
“…targeted at both the ISS-N1 element and exon 8 regulatory site produced a 2-fold increase in SMN mRNA and protein levels compared to single ASOs given alone (Pao et al., 2014), suggesting that combinatorial therapy may result in even better outcomes than already successful single treatments.”
Molecular, genetic and stem cell‐mediated therapeutic strategies for spinal muscular atrophy ( SMA )
Zanetta, C., Riboldi, G. M., Nizzardo, M., Simone, C., Faravelli, I., Bresolin, N., Comi, G. P., & Corti, S. P. (2014) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12224 · Cited by 28 · cited 2× · see citing works
“…inhibitors, viral SMN gene replacement, stem cells, and small molecules, are under current investigation (Duque et al., 2015; Van Meerbeke et al., 2013; Zanetta et al., 2014), the early success of ASOs in clinical studies will likely make this approach a benchmark to which others are compared.”
Solomonov, Y., Hadad, N., & Lévy, R. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0602-y · Cited by 26 · cited 3× · see citing works
“, 2013), phospholipase A2a (Solomonov et al., 2016), p75 (Turner et al.”
Younis, H. S., Vickers, T. J., Levin, A. A., & Henry, S. P. (2006) · Journal of Immunotoxicology · doi:10.1080/15476910600718236 · Cited by 23 · cited 1× · see citing works
“Both 20-O-methyl and 20-O-methoxyethyl modifications are commonly used in preclinical research and clinical trials. common in particular base sequences) are potent immune activators (Younis et al., 2006) and, therefore, are often avoided in designing ASOs for in vivo application.”
Gotkine, M., Leah, R., Einstein, O., Oded, A., Argov, Z., & Rosenmann, H. (2013) · BioMed Research International · doi:10.1155/2013/845345 · Cited by 20 · cited 2× · see citing works
“Other preclinical studies have identified acetylcholine (Gotkine et al., 2013), phospholipase A2a (Solomonov et al.”
A Negatively-Acting Bifunctional RNA Increases Survival Motor Neuron in vitro and in vivo
Dickson, A., Osman, E. Y., & Lorson, C. L. (2008) · Human Gene Therapy · doi:10.1089/hgt.2008.067 · Cited by 18 · see citing works
Peptide Nucleic Acids Targeted to the Amyloid Precursor Protein
McMahon, B. M., Stewart, J. A., Fauq, A. H., Younkin, S. G., Younkin, L. H., & Richelson, E. (2003) · Journal of Molecular Neuroscience · doi:10.1385/jmn:20:3:261 · Cited by 8 · see citing works
FDA approves orphan drug for inherited cholesterol disorder
reports, S. (2013) · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Agrawal S Kandimalla ER 2004 Role of Toll-like receptors in antisense and siRNA [corrected] Nat Biotechnol 22 1533 1537 15583662
- Butovsky O Jedrychowski MP Cialic R Krasemann S Murugaiyan G Fanek Z Greco DJ Wu PM Doykan CE Kiner O 2014 Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice Ann Neurol PMC4432483 25381879
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Sorted by citations
Protein Phase Separation: A New Phase in Cell Biology
Boeynaems, S., Alberti, S., Fawzi, N. L., Mittag, T., Polymenidou, M., Rousseau, F., Schymkowitz, J. W. H., Shorter, J., Wolozin, B. L., Bosch, L. V. D., et al. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.004 · Cited by 1,954 · see citing works
“Although ASOs targeting pathological proteins were successful in different mouse models [131], their application is limited to nonessential proteins.”
BackgroundNovel genes associated with amyotrophic lateral sclerosis: diagnostic and clinical implications
Chia, R., Chiò, A., & Traynor, B. J. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30401-5 · Cited by 576 · see citing works
Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing
Boland, B., Yu, W. H., Corti, O., Mollereau, B., Henriques, A., Bézard, E., Pastores, G., Rubinsztein, D. C., Nixon, R. A., Duchen, M. R., et al. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.109 · Cited by 552 · see citing works
ALS Genetics: Gains, Losses, and Implications for Future Therapies
Kim, G., Gautier, O., Tassoni-Tsuchida, E., Ma, X. R., & Gitler, A. D. (2020) · Neuron · doi:10.1016/j.neuron.2020.08.022 · Cited by 370 · see citing works
“Due to intrathecal injection of ASOs for wide distribution throughout the central nervous system (Schoch and Miller, 2017), most patients exhibited lumbar puncture-related adverse events (Miller et al.”
BackgroundDelivery of oligonucleotide‐based therapeutics: challenges and opportunities
Hammond, S. M., Aartsma-Rus, A. M., Alves, S., Borgos, S. E., Buijsen, R. A. M., Collin, R. W. J., Covello, G., Denti, M. A., Desviat, L. R., Echevarría, L., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202013243 · Cited by 395 · see citing works
“Animal models have been vital for determining in vivo efficacy of ONs, tissue-specific delivery, and optimising the route of administration for systemic and neurological diseases (Schoch & Miller, 2017; Buijsen et al, 2019).”
BackgroundAPOE and Alzheimer’s Disease: From Lipid Transport to Physiopathology and Therapeutics
Husain, M. A., Laurent, B., & Plourde, M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.630502 · Cited by 353 · see citing works
“Instead of using an antibody to neutralize apoE4, another strategy is to use antisense oligonucleotides (ASO) which can target APOE4 mRNA and decrease its expression (Schoch and Miller, 2017).”
BackgroundSpinocerebellar ataxia: an update
Sullivan, R., Yau, W. Y., O’Connor, E., & Houlden, H. (2018) · Journal of Neurology · doi:10.1007/s00415-018-9076-4 · Cited by 353 · see citing works
Mummery, C. J., Börjesson-Hanson, A., Blackburn, D. J., Vijverberg, E. G. B., De Deyn, P. P., Ducharme, S., Jonsson, M., Schneider, A., Rinne, J. O., Ludolph, A. C., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02326-3 · Cited by 347 · see citing works
“However, at steady state with respect to both ASO distribution and the production and elimination of tau, lowered CSF tau levels should index the reduction of newly synthesized tau 21,22,37 .”
Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery
Kim, B., Park, J., & Sailor, M. J. (2019) · Advanced Materials · doi:10.1002/adma.201903637 · Cited by 301 · see citing works
Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions
Nussbacher, J. K., Tabet, R., Yeo, G. W.-M., & Lagier‐Tourenne, C. (2019) · Neuron · doi:10.1016/j.neuron.2019.03.014 · Cited by 264 · see citing works
“The latter is most frequently used and currently under testing in several clinical trials (Schoch and Miller, 2017).”
BackgroundMethodTau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategies
Chang, C.-W., Shao, E., & Mucke, L. (2021) · Science · doi:10.1126/science.abb8255 · Cited by 263 · see citing works
“ASOs can also be used to modulate alternative splicing, a strategy that could help lower the abundance of the most pathogenic isoforms of tau (140), which may differ across tauopathies (1, 15).”
BackgroundBioconjugated Oligonucleotides: Recent Developments and Therapeutic Applications
Benizri, S., Gissot, A., Martin, A., Vialet, B., Grinstaff, M. W., & Barthélémy, P. (2019) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.8b00761 · Cited by 233 · see citing works
Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases
Wu, Y.-Y., & Kuo, H.-C. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00636-z · Cited by 213 · see citing works
Scoles, D. R., Minikel, E. V., & Pulst, S. M. (2019) · Neurology Genetics · doi:10.1212/nxg.0000000000000323 · Cited by 201 · see citing works
“A reformulated version of the drug designated IONIS-SOD1Rx (BIIB067) is presently undergoing phase 1 clinical trials by Ionis Pharmaceuticals and Biogen.(53)”
RNA Dysregulation in Amyotrophic Lateral Sclerosis
Butti, Z., & Patten, S. A. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2018.00712 · Cited by 195 · see citing works
“Furthermore, RNA-targeted therapies are currently intensively being evaluated as potential strategies for treating this ALS (Schoch and Miller, 2017; Mathis and Le Masson, 2018).”
BackgroundAge-dependent SMN expression in disease-relevant tissue and implications for SMA treatment
Ramos, D. M., d’Ydewalle, C. V. O., Gabbeta, V., Dakka, A., Klein, S., Norris, D. A., Matson, J. E., Taylor, S. J., Zaworski, P. G., Prior, T. W., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci124120 · Cited by 190 · see citing works
“The data reported here have important implications for optimization of therapeutics for SMA patients, but also highlight the importance of implementing such expedited autopsy programs to collect high-quality human CNS tissues in patients with other neurological diseases being targeted with novel gene targeting therape…”
BackgroundEmerging New Concepts of Degrader Technologies
Ding, Y., Fei, Y., & Lu, B. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.04.005 · Cited by 204 · see citing works
“One possible approach is gene therapy: gene silencing through nucleic acid-based RNA- or DNAtargeting reagents such as antisense oligonucleotides (ASOs) and genome-editing reagents, respectively [5,6] (Figure 1A).”
BackgroundGene therapy for ALS: A review
Amado, D. A., & Davidson, B. L. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.04.008 · Cited by 192 · see citing works
“Recently, various modifications have been made to increase ASO stability, protect against nuclease degradation, improve cellular uptake, recruit RNase H, and reduce immunogenicity.(64) Although they do not cross the blood-brain barrier, ASOs achieve widespread CNS distribution after i.”
BackgroundLactate from astrocytes fuels learning-induced mRNA translation in excitatory and inhibitory neurons
Descalzi, G., Gao, V., Steinman, M. Q., Suzuki, A., & Alberini, C. M. (2019) · Communications Biology · doi:10.1038/s42003-019-0495-2 · Cited by 188 · see citing works
Therapeutic landscape for Batten disease: current treatments and future prospects
Johnson, T. B., Cain, J. T., White, K. A., Ramirez‐Montealegre, D., Pearce, D. A., & Weimer, J. M. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0138-8 · Cited by 185 · see citing works
Chen, X., & Mobley, W. C. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00446 · Cited by 174 · see citing works
“Given restricted CNS access of peripherally administered ASOs, intrathecal delivery of ASOs may be required; this mode of delivery has recently been shown to be effective in treating neurodegenerative disorders (Schoch and Miller, 2017).”
BackgroundTherapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease
Williams, T., Borchelt, D., & Chakrabarty, P. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-0358-9 · Cited by 166 · see citing works
“Combined with the successful ASO based therapies being tested in Huntington’s and Amyotrophic Lateral Sclerosis (ALS) patients and the latest developments in ASO chemistry that can dramatically improve its pharmacokinetic and pharmacodynamic properties, ASO based therapies do have potential as promising future therape…”
BackgroundLafora disease — from pathogenesis to treatment strategies
Nitschké, F., Ahonen, S., Nitschke, S., Mitra, S., & Minassian, B. A. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0057-0 · Cited by 169 · see citing works
Coyne, A. N., Baskerville, V., Zaepfel, B. L., Dickson, D. W., Rigo, F., Bennett, F., Lusk, C. P., & Rothstein, J. D. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe1923 · Cited by 143 · see citing works
“ASOs are now used as a therapeutic strategy to reduce mRNA and protein expression of genes of interests (40, 41).”
BackgroundTargeting RNA : A Transformative Therapeutic Strategy
Yin, W., & Rogge, M. C. (2019) · Clinical and Translational Science · doi:10.1111/cts.12624 · Cited by 147 · see citing works
“, scoliosis and spinal fusion) are the common delivery methods of antisense oligonucleotides in the clinic.(28,60) However, less invasive methods, such as i.”
BackgroundMethodInfluentialOligonucleotide therapy mitigates disease in spinocerebellar ataxia type 3 mice
McLoughlin, H. S., Moore, L. R., Chopra, R., Komlo, R., McKenzie, M., Blumenstein, K. G., Zhao, H. T., Kordasiewicz, H. B., Shakkottai, V. G., & Paulson, H. L. (2018) · Annals of Neurology · doi:10.1002/ana.25264 · Cited by 140 · see citing works
“Gliosis occurs in SCA3(3,30) and can also be a potential adverse effect of ASO treatment.(31) To determine the tolerability of ASOs at increasing doses, treated mice were assessed for astrogliosis and microgliosis 4 weeks after treatment.”
BackgroundNEAT1 and paraspeckles in neurodegenerative diseases: A missing lnc found?
An, H., Williams, N. G., & Shelkovnikova, T. A. (2018) · Non-coding RNA Research · doi:10.1016/j.ncrna.2018.11.003 · Cited by 139 · see citing works
“ASOs are currently being explored as possible therapeutic options for monogenic NDDs [140].”
BackgroundBarker, S. J., Thayer, M. B., Kim, C., Tatarakis, D., Simon, M. J., Dial, R., Nilewski, L., Wells, R. C., Zhou, Y., Afetian, M., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adi2245 · Cited by 142 · see citing works
Nagata, T., Dwyer, C. A., Yoshida‐Tanaka, K., Ihara, K., Ohyagi, M., Kaburagi, H., Miyata, H., Ebihara, S., Yoshioka, K., Ishii, T., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00972-x · Cited by 140 · see citing works
CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma
Liu, S. J., Malatesta, M., Lien, B. V., Saha, P., Thombare, S. S., Hong, S. J., Pedraza, L., Koontz, M., Seo, K., Horlbeck, M. A., et al. (2020) · Genome biology · doi:10.1186/s13059-020-01995-4 · Cited by 142 · see citing works
Genetics, Mechanisms, and Therapeutic Progress in Polyglutamine Spinocerebellar Ataxias
Buijsen, R. A. M., Toonen, L. J. A., Gardiner, S. L., & van Roon‐Mom, W. (2019) · Neurotherapeutics · doi:10.1007/s13311-018-00696-y · Cited by 136 · see citing works
Antisense oligonucleotides in neurological disorders
Wurster, C. D., & Ludolph, A. C. (2018) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756286418776932 · Cited by 131 · see citing works
Friedrich, J., Kordasiewicz, H. B., O’Callaghan, B., Handler, H. P., Wagener, C., Duvick, L., Swayze, E. E., Rainwater, O., Hofstra, B., Benneyworth, M., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.123193 · Cited by 121 · see citing works
Vidovic, D., Huynh, T. T., Konda, P., Dean, C. A., Cruickshank, B. M., Sultan, M., Coyle, K. M., Gujar, S. A., & Marcato, P. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0362-1 · Cited by 121 · see citing works
Humanising the mouse genome piece by piece
Zhu, F., Nair, R., Fisher, E., & Cunningham, T. J. (2019) · Nature Communications · doi:10.1038/s41467-019-09716-7 · Cited by 110 · see citing works
A perspective on oligonucleotide therapy: Approaches to patient customization
Thakur, S., Sinhari, A., Jain, P., & Jadhav, H. R. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1006304 · Cited by 114 · see citing works
The informed road map to prevention of Alzheimer Disease: a call to arms
McDade, E., Llibre-Guerra, J. J., Holtzman, D. M., Morris, J. C., & Bateman, R. J. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00467-y · Cited by 89 · see citing works
“neurodegeneration in tauopathy mouse models [80, 81].”
Antisense oligonucleotides: absorption, distribution, metabolism, and excretion
Shadid, M., Badawi, M. A., & Abulrob, A. (2021) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2021.1992382 · Cited by 111 · see citing works
Clinical Trials in Alzheimer’s Disease: A Hurdle in the Path of Remedy
Oxford, A. E., Stewart, E. S., & Rohn, T. T. (2020) · International Journal of Alzheimer s Disease · doi:10.1155/2020/5380346 · Cited by 109 · see citing works
“Additionally, ASOs find limitations in their ability, or relative lack thereof, to cross the BBB and interact with the appropriate targets [107].”
BackgroundAntisense Therapy for a Common Corneal Dystrophy Ameliorates TCF4 Repeat Expansion-Mediated Toxicity
Zarouchlioti, C., Sanchez-Pintado, B., Hafford‐Tear, N. J., Klein, P., Lišková, P., Dulla, K., Semo, M., Vugler, A., Muthusamy, K., Ďuďáková, Ľ., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.02.010 · Cited by 101 · see citing works
Antisense Oligonucleotides for the Study and Treatment of ALS
Boros, B. D., Schoch, K. M., Kreple, C. J., & Miller, T. M. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01247-2 · Cited by 100 · see citing works
“The widespread distribution of ASO throughout the brain and spinal cord as demonstrated in this first study was unexpected given that ASOs are relatively large molecules and highly charged [8].”
BackgroundInfluentialSelf-citationGene Therapy for ALS—A Perspective
Cappella, M., Ciotti, C., Cohen-Tannoudji, M., & Biferi, M. G. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184388 · Cited by 96 · see citing works
“, DNA pl smids, RNA- or DNA-based oligonucleotid s, or silencing RNA, can be directly delivered to the host cell or they can be chemically modified to enhance their stability [14,15].”
BackgroundInfluentialNuclear pore complexes — a doorway to neural injury in neurodegeneration
Coyne, A. N., & Rothstein, J. D. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00653-6 · Cited by 96 · see citing works
Repeat-associated non-ATG (RAN) translation
Cleary, J. D., Pattamatta, A., & Ranum, L. P. W. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.r118.003237 · Cited by 95 · see citing works
“ASO strategies are also being developed for other expansion disorders, including SCA2, SCA3, and C9ORF72 (168, 169).”
BackgroundModulation of Brain Hyperexcitability: Potential New Therapeutic Approaches in Alzheimer’s Disease
Toniolo, S., Sen, A., & Husain, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239318 · Cited by 94 · see citing works
Tsoumpra, M. K., Fukumoto, S., Matsumoto, T., Takeda, S., Wood, M. J. A., & Aoki, Y. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.06.036 · Cited by 91 · see citing works
“Another 2ʹ-MOE ASO compound targeting SOD1 (IONIS-SOD1Rx, BIIB067) was investigated in a placebo-controlled phase I/II trial [222] in order to establish dosage and address safety issues and is currently in phase III clinical trial (NCT02623699).”
MethodMilazzo, C., Mientjes, E., Wallaard, I., Rasmussen, S. V., Erichsen, K. D., Kakunuri, T., van der Sman, A. S. E., Kremer, T., Miller, M. T., Hoener, M. C., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.145991 · Cited by 89 · see citing works
“, Huntington disease, amyotrophic lateral sclerosis, and spinal muscular atrophy) (14).”
BackgroundTwo breakthrough gene-targeted treatments for spinal muscular atrophy: challenges remain
Sumner, C. J., & Crawford, T. O. (2018) · Journal of Clinical Investigation · doi:10.1172/jci121658 · Cited by 88 · see citing works
PTB/nPTB: master regulators of neuronal fate in mammals
Hu, J., Qian, H., Xue, Y., & Fu, X. (2018) · Biophysics Reports · doi:10.1007/s41048-018-0066-y · Cited by 85 · see citing works
The clinical trial landscape in amyotrophic lateral sclerosis—Past, present, and future
Wobst, H. J., Mack, K. L., Brown, D. G., Brandon, N. J., & Shorter, J. (2020) · Medicinal Research Reviews · doi:10.1002/med.21661 · Cited by 83 · see citing works
“ASOs exert their therapeutic effects either by targeting RNAs for degradation, correcting splicing defects or sequestering miRNA.(185) They are particularly attractive for the treatment of diseases known”
BackgroundLuo, M., Lee, L. K. C., Peng, B., Choi, C. H. J., Tong, W. Y., & Voelcker, N. H. (2022) · Advanced Science · doi:10.1002/advs.202201740 · Cited by 81 · see citing works
Kim, M. E., & Lee, J. S. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb47010008 · Cited by 79 · see citing works
“ASOs are a promising treatment for chronic neuroinflammation because of their high specificity and relatively low immunogenicity; nevertheless, problems of cost and CNS administration still need to be resolved [69,70].”
Oligonucleotides to the (Gene) Rescue: FDA Approvals 2017–2019
Rüger, J., Ioannou, S., Castanotto, D., & Stein, C. A. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.10.009 · Cited by 77 · see citing works
Non-coding RNAs in Nervous System Development and Disease
Salvatori, B., Biscarini, S., & Morlando, M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00273 · Cited by 73 · see citing works
Alarcón-Arís, D., Pavia-Collado, R., Miquel-Rio, L., Cóppola-Segovia, V., Ferrés‐Coy, A., Ruiz‐Bronchal, E., Galofré, M., Paz, V., Campa, L., Revilla, R., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102944 · Cited by 76 · see citing works
The long non‐coding RNA landscape in triple‐negative breast cancer
Zhang, W., Guan, X., & Tang, J. (2020) · Cell Proliferation · doi:10.1111/cpr.12966 · Cited by 73 · see citing works
Biscans, A., Caiazzi, J., Davis, S. M., McHugh, N., Sousa, J., & Khvorova, A. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa595 · Cited by 68 · see citing works
“Indeed, optimization of PO/PS content for tricycloDNA ASOs (in Duchenne Muscular Dystrophy models) (66), and for oligonucleotides in the central nervous system has already been done, and is now a widely used strategy to achieve optimal efficacy, stability, safety (67).”
MethodMendonça, M. C. P., Kont, A., Aburto, M. R., Cryan, J. F., & O’Driscoll, C. M. (2021) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c01238 · Cited by 73 · see citing works
Antisense oligonucleotides and other genetic therapies made simple
Rossor, A. M., Reilly, M. M., & Sleigh, J. N. (2018) · Practical Neurology · doi:10.1136/practneurol-2017-001764 · Cited by 73 · see citing works
Oligonucleotide therapeutics in neurodegenerative diseases
Scoles, D. R., & Pulst, S. M. (2018) · RNA Biology · doi:10.1080/15476286.2018.1454812 · Cited by 72 · see citing works
“Drug Indication Target ASO Chemistry Status Nusinersen Spinal muscular atrophy SMN2, exon-7 inclusion ASO, full 2 0-MOE FDA approved Eteplirsen Duchene’s muscular dystrophy DMD, exon-51 skipping Morpholino FDA approved IONIS-HTTRx Huntington disease HTT expression ASO gapmer Phase I/II clinical trial IONIS-SOD1Rx SOD1…”
Silva, A. C., Lobo, D. D., Martins, I. M., Lopes, S., Henriques, C., Duarte, S., Dodart, J., Nobre, R. J., & de Almeida, L. P. (2019) · Brain · doi:10.1093/brain/awz328 · Cited by 72 · see citing works
Aberrant Phase Transitions: Side Effects and Novel Therapeutic Strategies in Human Disease
Verdile, V., Paola, E. D., & Paronetto, M. P. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00173 · Cited by 68 · see citing works
Emerging antisense oligonucleotide and viral therapies for amyotrophic lateral sclerosis
Ly, C. V., & Miller, T. M. (2018) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000594 · Cited by 69 · see citing works
Self-citationPornnoppadol, G., Bond, L. G., Lucas, M. J., Zupancic, J. M., Kuo, Y., Zhang, B., Greineder, C. F., & Tessier, P. M. (2023) · Cell chemical biology · doi:10.1016/j.chembiol.2023.09.008 · Cited by 70 · see citing works
Hagedorn, P., Brown, J. M., Easton, A. E., Pierdomenico, M., Jones, K. M., Olson, R. E., Mercer, S. E., Li, D., Loy, J. K., Høg, A. M., et al. (2022) · Nucleic Acid Therapeutics · doi:10.1089/nat.2021.0071 · Cited by 64 · see citing works
“Mouse models are often used to assess safety and therapeutic utility, and to establish pharmacodynamic and pharmacokinetic parameters of ASOs under development [3].”
BackgroundApplication of Non-Viral Vectors in Drug Delivery and Gene Therapy
Ren, S., Wang, M., Wang, C., Wang, Y., Sun, C., Zeng, Z., Cui, H., & Zhao, X. (2021) · Polymers · doi:10.3390/polym13193307 · Cited by 65 · see citing works
Cas9-mediated replacement of expanded CAG repeats in a pig model of Huntington’s disease
Yan, S., Zheng, X., Lin, Y., Li, C., Liu, Z., Li, J., Tu, Z., Zhao, Y., Huang, C., Chen, Y., et al. (2023) · Nature Biomedical Engineering · doi:10.1038/s41551-023-01007-3 · Cited by 66 · see citing works
Biomolecular condensates: Formation mechanisms, biological functions, and therapeutic targets
Niu, X., Zhang, L., Wu, Y., Zong, Z., Wang, B., Liu, J., Zhang, L., & Zhou, F. (2023) · MedComm · doi:10.1002/mco2.223 · Cited by 64 · see citing works
Cideciyan, A. V., Jacobson, S. G., Ho, A. C., Garafalo, A. V., Román, A. J., Sumaroka, A., Krishnan, A. K., Świder, M., Schwartz, M. R., & Girach, A. (2021) · Nature Medicine · doi:10.1038/s41591-021-01297-7 · Cited by 63 · see citing works
miR-129-5p: A key factor and therapeutic target in amyotrophic lateral sclerosis
Loffreda, A., Nizzardo, M., Arosio, A., Ruepp, M., Calogero, R., Volinia, S., Galasso, M., Bendotti, C., Ferrarese, C., Lunetta, C., et al. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101803 · Cited by 58 · see citing works
Derbis, M., Kul, E., Niewiadomska, D., Sekrecki, M., Piasecka, A., Taylor, K., Hukema, R. K., Stork, O., & Sobczak, K. (2021) · Nature Communications · doi:10.1038/s41467-021-21021-w · Cited by 60 · see citing works
Piergentili, R., Gullo, G., Basile, G., Gulìa, C., Porrello, A., Cucinella, G., Marinelli, E., & Zaami, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411356 · Cited by 60 · see citing works
“mRNA sequences in the cell cytoplasm, in order to inhibit protein translation or to induce exon skipping were targeted by newly developed antisense oligonucleotides (ASOs) [143].”
BackgroundZeniya, S., Kuwahara, H., Daizo, K., Watari, A., Kondoh, M., Yoshida‐Tanaka, K., Kaburagi, H., Asada, K., Nagata, T., Nagahama, M., et al. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.05.010 · Cited by 59 · see citing works
Small interfering RNA from the lab discovery to patients' recovery
Caillaud, M., Madani, M. E., & Massaad-Massade, L. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.02.032 · Cited by 59 · see citing works
Nanotransducers for wireless neuromodulation
Li, X., Xiong, H., Rommelfanger, N. J., Xu, X., Youn, J., Slesinger, P. A., Hong, G., & Qin, Z. (2021) · Matter · doi:10.1016/j.matt.2021.02.012 · Cited by 59 · see citing works
Non-Viral Vector-Mediated Gene Therapy for ALS: Challenges and Future Perspectives
Ediriweera, G. R., Chen, L., Yerbury, J. J., Thurecht, K. J., & Vine, K. L. (2021) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.1c00297 · Cited by 56 · see citing works
Non-small molecule PROTACs (NSM-PROTACs): Protein degradation kaleidoscope
Ma, S., Ji, J., Tong, Y., Zhu, Y., Dou, J., Zhang, X., Xu, S., Zhu, T., Xu, X., You, Q., et al. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.02.022 · Cited by 57 · see citing works
Impact of increased <i>APP</i> gene dose in Down syndrome and the Dp16 mouse model
Sawa, M., Overk, C., Becker, A., Derse, D., Albay, R., Weldy, K., Salehi, A., Beach, T. G., Doran, E., Head, E., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12463 · Cited by 54 · see citing works
Shao, E., Chang, C.-W., Li, Z., Yu, X., Ho, K., Zhang, M., Wang, X., Simms, J., Lo, I., Speckart, J., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abm5527 · Cited by 54 · see citing works
The Impact of Mitochondrial Deficiencies in Neuromuscular Diseases
Cantó, J., Grau‐Junyent, J. M., & Garrabou, G. (2020) · Antioxidants · doi:10.3390/antiox9100964 · Cited by 53 · see citing works
“ASOs are short, synthetic single-stranded nucleic acids that bind targeted RNAs sequences to promote their degradation or modify splicing by impeding the binding of RNA splicing factors [153].”
BackgroundKorecka, J. A., Thomas, R., Hinrich, A. J., Moskites, A., Macbain, Z. K., Hallett, P. J., Ole Isacson, A., & Hastings, M. L. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.06.027 · Cited by 50 · see citing works
“With the striking success of ASO-based therapeutic strategy development, current research is focusing on new ASO delivery methods into the CNS, including oral, subcutaneous, and even intranasal delivery routes.(45) From this perspective, local administration into the CNS of highly specific and stable exon 41 skipping…”
BackgroundYang, A., Kantor, B., & Chiba‐Falek, O. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031244 · Cited by 50 · see citing works
“Another concern is the possibility of adverse side effects due to ASO-induced cellular toxicities and off-target effects in both sequence- and chemistrydependent manners [65].”
BackgroundInfluentialProtein Aggregation Inhibitors as Disease-Modifying Therapies for Polyglutamine Diseases
Minakawa, E. N., & Nagai, Y. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.621996 · Cited by 50 · see citing works
Krichevsky, A. M., & Uhlmann, E. J. (2019) · Neurotherapeutics · doi:10.1007/s13311-018-00702-3 · Cited by 47 · see citing works
Fan, N., Bian, X., Li, M., Chen, J., Wu, H., Peng, Q., Bai, H., Cheng, W., Kong, L., Ding, S., et al. (2022) · Science Advances · doi:10.1126/sciadv.abn7382 · Cited by 47 · see citing works
Spencer, B. J., Trinh, I., Rockenstein, E. M., Mante, M., Florio, J. B., Adame, A., El‐Agnaf, O. M. A., Kim, C., Masliah, E., & Rissman, R. A. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.03.001 · Cited by 46 · see citing works
Long non‐coding RNAs in motor neuron development and disease
Vangoor, V. R., Gomes‐Duarte, A., & Pasterkamp, R. J. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15198 · Cited by 42 · see citing works
“The application of ASOs could lead to adverse side effects, because of their off-target effects depending on the sequence and modification chemistry of the motifs used to stabilize the ASO-molecule for protection against cellular degradation (Schoch & Miller, 2017).”
BackgroundFrom basic research to the clinic: innovative therapies for ALS and FTD in the pipeline
Liščić, R. M., Alberici, A., Cairns, N. J., Romano, M., & Buratti, E. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00373-9 · Cited by 45 · see citing works
RNA Therapeutics: How Far Have We Gone?
Coutinho, M. F., Matos, L., Santos, J. I., & Alves, S. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-19966-1_7 · Cited by 44 · see citing works
Mendonsa, S., von Kuegelgen, N., Bujanić, L., & Chekulaeva, M. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab730 · Cited by 38 · see citing works
“Antisense oligos (ASO) are a promising therapeutic strategy to downregulate genes with toxic gain-of-function phenotype (reviewed in (46)).”
BackgroundUses for humanised mouse models in precision medicine for neurodegenerative disease
Nair, R., Corrochano, S., Gasco, S., Tibbit, C., Thompson, D., Maduro, C., Ali, Z., Fratta, P., Acevedo‐Arozena, A., Cunningham, T. J., et al. (2019) · Mammalian Genome · doi:10.1007/s00335-019-09807-2 · Cited by 41 · see citing works
Rothstein, J. D., Baskerville, V., Rapuri, S., Mehlhop, E., Jafar‐Nejad, P., Rigo, F., Bennett, F., Mizielinska, S., Isaacs, A. M., & Coyne, A. N. (2023) · Acta Neuropathologica · doi:10.1007/s00401-023-02652-3 · Cited by 40 · see citing works
“…for evaluating the efficacy of therapeutic strategies in the repair of TDP-43 functionality in the absence of TDP-43 aggregation and accumulation in the cytoplasm in ALS/FTD. ASOs are now a commonly used therapeutic modality to alter the expression of target genes in neurodegeneration [13, 42].”
BackgroundFAK-targeting PROTAC as a chemical tool for the investigation of non-enzymatic FAK function in mice
Gao, H., Zheng, C., Du, J., Wu, Y., Sun, Y., Han, C., Kee, K., & Rao, Y. (2020) · Protein & Cell · doi:10.1007/s13238-020-00732-8 · Cited by 40 · see citing works
Mechanisms and regulation underlying membraneless organelle plasticity control
Ismail, H., Liu, X., Yang, F., Li, J., Zahid, A., Dou, Z., Liu, X., & Yao, X. (2021) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjab028 · Cited by 39 · see citing works
“The key players in anomalous phase separation can be knocked down using ASOs, which has been demonstrated successfully in various mouse models (Schoch and Miller, 2017).”
BackgroundDupré, N., Gueniot, F., Domenga, V., Dubosclard, V., Nilles, C., Hill‐Eubanks, D. C., Morgenthaler-Roth, C., Nelson, M. T., Keime, C., Danglot, L., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci175789 · Cited by 39 · see citing works
Brown, J. M., Wasson, M. D., & Marcato, P. (2020) · Cells · doi:10.3390/cells9030763 · Cited by 37 · see citing works
“ASOs have demonstrated success in both animal models and human clinical trials, and strikingly, ASOs were recently FDA-approved for clinical use for neurodegenerative diseases [60].”
BackgroundInfluentialGene-Targeting Therapeutics for Neurological Disease: Lessons Learned from Spinal Muscular Atrophy
Ravi, B., Chan-Cortés, M. H., & Sumner, C. J. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-070119-115459 · Cited by 37 · see citing works
Byrnes, A. E., Domínguez, S. L., Yen, C., Laufer, B. I., Foreman, O., Reichelt, M., Lin, H., Sagolla, M. S., Hötzel, K., Ngu, H., et al. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.05.005 · Cited by 35 · see citing works
“Alternatively, ASO gapmers typically promote RNase H1 recruitment, which targets RNA for degradation and reduces protein expression.(2) Recent years have seen a marked increase in ASO development for the treatment of various neurodegenerative diseases.”
BackgroundProgress in the Use of Antisense Oligonucleotides for Vaccine Improvement
Batista-Duharte, A., Sendra, L., Herrero, M. J., Téllez-Martínez, D., Carlos, I. Z., & Aliño, S. F. (2020) · Biomolecules · doi:10.3390/biom10020316 · Cited by 36 · see citing works
“ASO toxicities including off-target effects can be both sequences- and chemistry-dependent, and thus, each ASO molecule must be considered independently during toxicological studies [159].”
BackgroundEdiriweera, G. R., Sivaram, A. J., Cowin, G., Brown, M. L., McAlary, L., Lum, J. S., Fletcher, N. L., Robinson, L., Simpson, J. D., Chen, L., et al. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.11.074 · Cited by 41 · see citing works
- Authors
- Schoch, K. M., & Miller, T. M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Miller, Timothy M.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 94
- Issue
- 6
- Pages
- 1056-1070
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5821515
- OpenAlex
- W2691085783
- Cited by
- 274
- References
- 128
- Citations by year
- 2026: 20 · 2025: 14 · 2024: 22 · 2023: 25 · 2022: 31 · 2021: 43 · 2020: 51 · 2019: 38 · 2018: 27 · 2017: 3
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH National Institute of Neurological Disorders and Stroke (R01NS097816)
- National Institute of Aging (R21AG044719)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- antisense oligonucleotides, neurodegenerative diseases, protein aggregation, RNA-targeted therapeutics, mouse model, clinical trials, protein dysfunction
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Disease Models, Animal, Drug Evaluation, Preclinical, Humans, Injections, Intraventricular, Injections, Spinal, Ribonucleases, RNA, Messenger, Oligonucleotides, Antisense, Neurodegenerative Diseases, Mice
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