{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:18:04Z","timestamp":1792009084665,"version":"4.4.0"},"reference-count":281,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T00:00:00Z","timestamp":1667606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intellectual and Developmental Disabilities Research Center at Kennedy Krieger","award":["NICHD P50 HD103538"],"award-info":[{"award-number":["NICHD P50 HD103538"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Antisense oligonucleotides (ASOs) are disease-modifying agents affecting protein-coding and noncoding ribonucleic acids. Depending on the chemical modification and the location of hybridization, ASOs are able to reduce the level of toxic proteins, increase the level of functional protein, or modify the structure of impaired protein to improve function. There are multiple challenges in delivering ASOs to their site of action. Chemical modifications in the phosphodiester bond, nucleotide sugar, and nucleobase can increase structural thermodynamic stability and prevent ASO degradation. Furthermore, different particles, including viral vectors, conjugated peptides, conjugated antibodies, and nanocarriers, may improve ASO delivery. To date, six ASOs have been approved by the US Food and Drug Administration (FDA) in three neurological disorders: spinal muscular atrophy, Duchenne muscular dystrophy, and polyneuropathy caused by hereditary transthyretin amyloidosis. Ongoing preclinical and clinical studies are assessing the safety and efficacy of ASOs in multiple genetic and acquired neurological conditions. The current review provides an update on underlying mechanisms, design, chemical modifications, and delivery of ASOs. The administration of FDA-approved ASOs in neurological disorders is described, and current evidence on the safety and efficacy of ASOs in other neurological conditions, including pediatric neurological disorders, is reviewed.<\/jats:p>","DOI":"10.3390\/pharmaceutics14112389","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T03:02:22Z","timestamp":1667790142000},"page":"2389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Antisense Oligonucleotide Therapy for the Nervous System: From Bench to Bedside with Emphasis on Pediatric Neurology"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1197-0833","authenticated-orcid":false,"given":"Man","family":"Amanat","sequence":"first","affiliation":[{"name":"Moser Center for Leukodystrophies, Kennedy Krieger Institute, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina L.","family":"Nemeth","sequence":"additional","affiliation":[{"name":"Moser Center for Leukodystrophies, Kennedy Krieger Institute, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amena Smith","family":"Fine","sequence":"additional","affiliation":[{"name":"Moser Center for Leukodystrophies, Kennedy Krieger Institute, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2558-7798","authenticated-orcid":false,"given":"Doris G.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Center for Genetic Muscle Disorders, Kennedy Krieger Institute, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Fatemi","sequence":"additional","affiliation":[{"name":"Moser Center for Leukodystrophies, Kennedy Krieger Institute, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1056\/NEJMoa042760","article-title":"Pegaptanib for neovascular age-related macular degeneration","volume":"351","author":"Gragoudas","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa1716153","article-title":"Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis","volume":"379","author":"Adams","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1056\/NEJMoa1913147","article-title":"Phase 3 trial of RNAi therapeutic givosiran for acute intermittent porphyria","volume":"382","author":"Balwani","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1056\/NEJM199602013340508","article-title":"Antisense-oligonucleotide therapy","volume":"334","author":"Askari","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_5","unstructured":"Vitravene Study Group (2002). A randomized controlled clinical trial of intravitreous fomivirsen for treatment of newly diagnosed peripheral cytomegalovirus retinitis in patients with AIDS. Am. J. Ophthalmol., 133, 467\u2013474."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1016\/j.jacc.2013.07.081","article-title":"Mipomersen, an apolipoprotein B synthesis inhibitor, reduces atherogenic lipoproteins in patients with severe hypercholesterolemia at high cardiovascular risk: A randomized, double-blind, placebo-controlled trial","volume":"62","author":"Thomas","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/ana.24555","article-title":"Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy","volume":"79","author":"Mendell","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_8","first-page":"1656","article-title":"Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure","volume":"127","author":"Richardson","year":"2016","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJMoa1702752","article-title":"Nusinersen versus sham control in infantile-onset spinal muscular atrophy","volume":"377","author":"Finkel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1056\/NEJMoa1716793","article-title":"Inotersen treatment for patients with hereditary transthyretin amyloidosis","volume":"379","author":"Benson","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1089\/nat.2021.0043","article-title":"Long-term safety and efficacy data of golodirsen in ambulatory patients with Duchenne muscular dystrophy amenable to exon 53 skipping: A first-in-human, multicenter, two-part, open-label, phase 1\/2 trial","volume":"32","author":"Servais","year":"2022","journal-title":"Nucleic Acid Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"eaan0713","DOI":"10.1126\/scitranslmed.aan0713","article-title":"Systemic administration of the antisense oligonucleotide NS-065\/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy","volume":"10","author":"Komaki","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/mus.27347","article-title":"Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: A randomized, double-blind, placebo-controlled, dose-titration trial","volume":"64","author":"Wagner","year":"2021","journal-title":"Muscle Nerve"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Adams, D., Tournev, I.L., Taylor, M.S., Coelho, T., Plant\u00e9-Bordeneuve, V., Berk, J.L., Gonz\u00e1lez-Duarte, A., Gillmore, J.D., Low, S.C., and Sekijima, Y. (2022). Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: A randomized clinical trial. Amyloid, 1\u20139.","DOI":"10.1080\/13506129.2022.2091985"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.ekir.2021.12.001","article-title":"Randomized Clinical Trial on the Long-Term Efficacy and Safety of Lumasiran in Patients with Primary Hyperoxaluria Type 1","volume":"7","author":"Hulton","year":"2022","journal-title":"Kidney Int. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1001\/jamacardio.2019.3502","article-title":"Effect of 1 or 2 doses of inclisiran on low-density lipoprotein cholesterol levels: One-year follow-up of the ORION-1 randomized clinical trial","volume":"4","author":"Ray","year":"2019","journal-title":"JAMA Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/S0006-291X(02)02013-2","article-title":"Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo","volume":"296","author":"Bertrand","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/108729003764097296","article-title":"Comparison of the suppressive effects of antisense oligonucleotides and siRNAs directed against the same targets in mammalian cells","volume":"13","author":"Miyagishi","year":"2003","journal-title":"Antisense Nucleic Acid Drug Dev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4417","DOI":"10.1093\/nar\/gkg649","article-title":"The activity of siRNA in mammalian cells is related to structural target accessibility: A comparison with antisense oligonucleotides","volume":"31","author":"Sczakiel","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7108","DOI":"10.1074\/jbc.M210326200","article-title":"Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents: A comparative analysis","volume":"278","author":"Vickers","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1093\/nar\/gkg139","article-title":"Antisense oligonucleotides targeted to the domain IIId of the hepatitis C virus IRES compete with 40S ribosomal subunit binding and prevent in vitro translation","volume":"31","author":"Chabas","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.1073\/pnas.85.14.5011","article-title":"Role of RNase H in hybrid-arrested translation by antisense oligonucleotides","volume":"85","author":"Walder","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11994","DOI":"10.1074\/jbc.272.18.11994","article-title":"2\u2032-O-(2-Methoxy) ethyl-modified anti-intercellular adhesion molecule 1 (ICAM-1) oligonucleotides selectively increase the ICAM-1 mRNA level and inhibit formation of the ICAM-1 translation initiation complex in human umbilical vein endothelial cells","volume":"272","author":"Baker","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/j.jaci.2021.09.039","article-title":"Targeting IgE polyadenylation signal with antisense oligonucleotides decreases IgE secretion and plasma cell viability","volume":"149","author":"Marchalot","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nbt.3589","article-title":"Translation efficiency of mRNAs is increased by antisense oligonucleotides targeting upstream open reading frames","volume":"34","author":"Liang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9528","DOI":"10.1093\/nar\/gkx632","article-title":"Antisense oligonucleotides targeting translation inhibitory elements in 5\u2032 UTRs can selectively increase protein levels","volume":"45","author":"Liang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"eaaz6100","DOI":"10.1126\/scitranslmed.aaz6100","article-title":"Antisense oligonucleotides increase Scn1a expression and reduce seizures and SUDEP incidence in a mouse model of Dravet syndrome","volume":"12","author":"Han","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.gene.2016.08.052","article-title":"Proximity of AUG sequences to initiation codon in genomic 5\u2032 UTR regulates mammalian protein expression","volume":"594","year":"2016","journal-title":"Gene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7507","DOI":"10.1073\/pnas.0810916106","article-title":"Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans","volume":"106","author":"Calvo","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.1038\/s41467-020-17093-9","article-title":"Antisense oligonucleotide modulation of non-productive alternative splicing upregulates gene expression","volume":"11","author":"Lim","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1016\/j.celrep.2017.08.012","article-title":"The functional impact of alternative splicing in cancer","volume":"20","author":"Godzik","year":"2017","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s40520-019-01360-x","article-title":"Alternative splicing in Alzheimer\u2019s disease","volume":"33","author":"Biamonti","year":"2021","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0959-437X(02)00303-9","article-title":"Familial dysautonomia","volume":"12","author":"Slaugenhaupt","year":"2002","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1203\/PDR.0b013e318194fd52","article-title":"Kinetin in familial dysautonomia carriers: Implications for a new therapeutic strategy targeting mRNA splicing","volume":"65","author":"Goldberg","year":"2009","journal-title":"Pediatr. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1089\/hum.2012.225","article-title":"Antisense oligonucleotides for the treatment of spinal muscular atrophy","volume":"24","author":"Porensky","year":"2013","journal-title":"Hum. Gene Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4114","DOI":"10.1073\/pnas.0633863100","article-title":"Bifunctional antisense oligonucleotides provide a trans-acting splicing enhancer that stimulates SMN2 gene expression in patient fibroblasts","volume":"100","author":"Skordis","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1042\/BJ20110795","article-title":"Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA","volume":"441","author":"Dooves","year":"2012","journal-title":"Biochem. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1101\/gad.1384005","article-title":"A human, ATP-independent, RISC assembly machine fueled by pre-miRNA","volume":"19","author":"Maniataki","year":"2005","journal-title":"Genes Dev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.gde.2013.01.004","article-title":"miRNA profiling of cancer","volume":"23","author":"Croce","year":"2013","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12935-015-0185-1","article-title":"MicroRNA (miRNA) in cancer","volume":"15","author":"Reddy","year":"2015","journal-title":"Cancer Cell Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1007\/s12032-012-0376-8","article-title":"MicroRNA-21 gene and cancer","volume":"30","author":"Huang","year":"2013","journal-title":"Med. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/2043-9113-3-17","article-title":"The multiple roles of microRNA-155 in oncogenesis","volume":"3","author":"Higgs","year":"2013","journal-title":"J. Clin. Bioinform."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1126\/science.1113329","article-title":"Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA","volume":"309","author":"Jopling","year":"2005","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1089\/hum.2018.205","article-title":"Dysregulated expression of microRNA-21 and disease-related genes in human patients and in a mouse model of Alport syndrome","volume":"30","author":"Guo","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/ncomms2090","article-title":"The miRNA-212\/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy","volume":"3","author":"Ucar","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/mt.2008.205","article-title":"Guidelines for antisense oligonucleotide design and insight into splice-modulating mechanisms","volume":"17","author":"Hirschi","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1093\/nar\/gkg595","article-title":"Mfold web server for nucleic acid folding and hybridization prediction","volume":"31","author":"Zuker","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.1093\/nar\/gkg599","article-title":"Vienna RNA secondary structure server","volume":"31","author":"Hofacker","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-11-129","article-title":"RNAstructure: Software for RNA secondary structure prediction and analysis","volume":"11","author":"Reuter","year":"2010","journal-title":"BMC Bioinform."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5407","DOI":"10.1038\/s41467-019-13395-9","article-title":"RNA secondary structure prediction using an ensemble of two-dimensional deep neural networks and transfer learning","volume":"10","author":"Singh","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1093\/nar\/gkg612","article-title":"RNAsoft: A suite of RNA secondary structure prediction and design software tools","volume":"31","author":"Andronescu","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/j.1440-1681.2006.04403.x","article-title":"Antisense oligonucleotides: From design to therapeutic application","volume":"33","author":"Chan","year":"2006","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1093\/nar\/24.10.1901","article-title":"Potent antisense oligonucleotides to the human multidrug resistance-1 mRNA are rationally selected by mapping RNA-accessible sites with oligonucleotide libraries","volume":"24","author":"Peng","year":"1996","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.1093\/nar\/28.15.2862","article-title":"Identification of sequence motifs in oligonucleotides whose presence is correlated with antisense activity","volume":"28","author":"Matveeva","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"W43","DOI":"10.1093\/nar\/gkm234","article-title":"OligoCalc: An online oligonucleotide properties calculator","volume":"35","author":"Kibbe","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"W5","DOI":"10.1093\/nar\/gkn201","article-title":"NCBI BLAST: A better web interface","volume":"36","author":"Johnson","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"9193","DOI":"10.1093\/nar\/17.22.9193","article-title":"RNase H cleavage of RNA hybridized to oligonucleotides containing methylphosphonate, phosphorothioate and phosphodiester bonds","volume":"17","author":"Furdon","year":"1989","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1089\/oli.1.2000.10.117","article-title":"Phosphorothioate oligodeoxynucleotides: What is their origin and what is unique about them?","volume":"10","author":"Eckstein","year":"2000","journal-title":"Antisense Nucleic Acid Drug Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1093\/nar\/18.7.1763","article-title":"The stability, toxicity and effectiveness of unmodified and phosphorothioate antisense oligodeoxynucleotides in Xenopus oocytes and embryos","volume":"18","author":"Woolf","year":"1990","journal-title":"Nucleic Acids Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1089\/ard.1995.5.131","article-title":"Characterization of binding sites, extent of binding, and drug interactions of oligonucleotides with albumin","volume":"5","author":"Srinivasan","year":"1995","journal-title":"Antisense Res. Dev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"14598","DOI":"10.1038\/s41598-017-15178-y","article-title":"Phosphodiester backbone of the CpG motif within immunostimulatory oligodeoxynucleotides augments activation of Toll-like receptor 9","volume":"7","author":"Pohar","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0167-4781(99)00140-2","article-title":"A review of issues in the pharmacokinetics and toxicology of phosphorothioate antisense oligonucleotides","volume":"1489","author":"Levin","year":"2000","journal-title":"Biochim. Et Biophys. Acta-Gene Struct. Expr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1089\/oli.1.1999.9.53","article-title":"Boranophosphates support the RNase H cleavage of polyribonucleotides","volume":"9","author":"Rait","year":"1999","journal-title":"Antisense Nucleic Acid Drug Dev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1081\/NCN-120022823","article-title":"RNase H activation by stereoregular boranophosphate oligonucleotide","volume":"22","author":"Wang","year":"2003","journal-title":"Nucl. Nucl. Nucleic Acids"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/nar\/26.2.431","article-title":"Zwitterionic oligodeoxyribonucleotide N3\u2032\u2192 P5\u2032 phosphoramidates: Synthesis and properties","volume":"26","author":"Mignet","year":"1998","journal-title":"Nucleic Acids Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/83489","article-title":"Phosphoramidate oligonucleotides as potent antisense molecules in cells and in vivo","volume":"19","author":"Faria","year":"2001","journal-title":"Nat. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1073\/pnas.1813376116","article-title":"Mesyl phosphoramidate antisense oligonucleotides as an alternative to phosphorothioates with improved biochemical and biological properties","volume":"116","author":"Miroshnichenko","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3966","DOI":"10.1073\/pnas.94.8.3966","article-title":"Antileukemia effect of c-myc N3\u2032\u2192 P5\u2032 phosphoramidate antisense oligonucleotides in vivo","volume":"94","author":"Skorski","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9045","DOI":"10.1021\/bi050574m","article-title":"Probing the influence of stereoelectronic effects on the biophysical properties of oligonucleotides: Comprehensive analysis of the RNA affinity, nuclease resistance, and crystal structure of ten 2 \u2018-O-ribonucleic acid modifications","volume":"44","author":"Egli","year":"2005","journal-title":"Biochemistry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1093\/nar\/30.9.1911","article-title":"Design of antisense oligonucleotides stabilized by locked nucleic acids","volume":"30","author":"Kurreck","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"11043","DOI":"10.1038\/s41598-017-09147-8","article-title":"LNA effects on DNA binding and conformation: From single strand to duplex and triplex structures","volume":"7","author":"Xu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1124\/jpet.115.226969","article-title":"Identification and characterization of modified antisense oligonucleotides targeting DMPK in mice and nonhuman primates for the treatment of myotonic dystrophy type 1","volume":"355","author":"Pandey","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jconrel.2018.12.030","article-title":"Fibrin-hyaluronic acid hydrogel-based delivery of antisense oligonucleotides for ADAMTS5 inhibition in co-delivered and resident joint cells in osteoarthritis","volume":"294","author":"Garcia","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"10166","DOI":"10.1021\/bi101208k","article-title":"Allele-selective inhibition of mutant huntingtin expression with antisense oligonucleotides targeting the expanded CAG repeat","volume":"49","author":"Gagnon","year":"2010","journal-title":"Biochemistry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"16509","DOI":"10.1073\/pnas.1909649117","article-title":"Inhibition of DUX4 expression with antisense LNA gapmers as a therapy for facioscapulohumeral muscular dystrophy","volume":"117","author":"Lim","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Kuespert, S., Heydn, R., Peters, S., Wirkert, E., Meyer, A.L., Sieb\u00f6rger, M., Johannesen, S., Aigner, L., Bogdahn, U., and Bruun, T.H. (2020). Antisense oligonucleotide in LNA-gapmer design targeting TGFBR2\u2014A key single gene target for safe and effective inhibition of TGF\u03b2 signaling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21061952"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/bjh.15547","article-title":"Cobomarsen, an oligonucleotide inhibitor of miR-155, co-ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T-cell lymphoma","volume":"183","author":"Seto","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1128\/AAC.04220-14","article-title":"In vitro antiviral activity and preclinical and clinical resistance profile of miravirsen, a novel anti-hepatitis C virus therapeutic targeting the human factor miR-122","volume":"59","author":"Ottosen","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1172\/JCI75852","article-title":"Anti\u2013microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways","volume":"125","author":"Gomez","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"721","DOI":"10.2147\/DDDT.S288859","article-title":"The risks of miRNA therapeutics: In a drug target perspective","volume":"15","author":"Zhang","year":"2021","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"12976","DOI":"10.1021\/ja982325+","article-title":"Hybrids of RNA and arabinonucleic acids (ANA and 2 \u2018F-ANA) are substrates of ribonuclease H","volume":"120","author":"Damha","year":"1998","journal-title":"J. Am. Chem. Soc."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.omtn.2019.07.001","article-title":"Dual mechanisms of action of self-delivering, anti-HIV-1 FANA oligonucleotides as a potential new approach to HIV therapy","volume":"17","author":"Takahashi","year":"2019","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5894","DOI":"10.1038\/s41467-020-19692-y","article-title":"Endogenous antisense RNA curbs CD39 expression in Crohn\u2019s disease","volume":"11","author":"Harshe","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.pupt.2008.08.001","article-title":"Advantageous toxicity profile of inhaled antisense oligonucleotides following chronic dosing in non-human primates","volume":"21","author":"Guimond","year":"2008","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.celrep.2019.12.011","article-title":"Targeting the oncogenic long non-coding RNA SLNCR1 by blocking its sequence-specific binding to the androgen receptor","volume":"30","author":"Schmidt","year":"2020","journal-title":"Cell Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"101771","DOI":"10.1016\/j.isci.2020.101771","article-title":"LET-Dependent Low Dose and Synergistic Inhibition of Human Angiogenesis by Charged Particles: Validation of miRNAs that Drive Inhibition","volume":"23","author":"Wuu","year":"2020","journal-title":"IScience"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"ENEURO.0338-20.2021","DOI":"10.1523\/ENEURO.0338-20.2021","article-title":"Use of a self-delivering Anti-CCL3 FANA Oligonucleotide as an innovative approach to target inflammation after Spinal Cord Injury","volume":"8","author":"Pelisch","year":"2021","journal-title":"eNeuro"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1021\/acs.accounts.1c00125","article-title":"2\u2032-Fluoro-arabinonucleic Acid (FANA): A Versatile Tool for Probing Biomolecular Interactions","volume":"54","author":"Damha","year":"2021","journal-title":"Acc. Chem. Res."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Dhuri, K., Bechtold, C., Quijano, E., Pham, H., Gupta, A., Vikram, A., and Bahal, R. (2020). Antisense oligonucleotides: An emerging area in drug discovery and development. J. Clin. Med., 9.","DOI":"10.3390\/jcm9062004"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/ejhg.2012.261","article-title":"In vitro antisense therapeutics for a deep intronic mutation causing Neurofibromatosis type 2","volume":"21","author":"Castellanos","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Aung-Htut, M.T., McIntosh, C.S., West, K.A., Fletcher, S., and Wilton, S.D. (2019). In vitro validation of phosphorodiamidate morpholino oligomers. Molecules, 24.","DOI":"10.3390\/molecules24162922"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1038\/sj.gt.3302800","article-title":"Antisense oligonucleotide-induced exon skipping restores dystrophin expression in vitro in a canine model of DMD","volume":"13","author":"Mcclorey","year":"2006","journal-title":"Gene Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1126\/science.1279811","article-title":"Antisense and antigene properties of peptide nucleic acids","volume":"258","author":"Hanvey","year":"1992","journal-title":"Science"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1385\/MB:26:3:233","article-title":"PNA technology","volume":"26","author":"Nielsen","year":"2004","journal-title":"Mol. Biotechnol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1093\/nar\/24.3.494","article-title":"Antisense properties of duplex-and triplex-forming PNAs","volume":"24","author":"Knudsen","year":"1996","journal-title":"Nucleic Acids Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1021\/bc050283q","article-title":"Evaluation of cell-penetrating peptides (CPPs) as vehicles for intracellular delivery of antisense peptide nucleic acid (PNA)","volume":"17","author":"Bendifallah","year":"2006","journal-title":"Bioconjugate Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1038\/sj.mt.6300255","article-title":"A novel cell-penetrating peptide, M918, for efficient delivery of proteins and peptide nucleic acids","volume":"15","author":"Johansson","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3197","DOI":"10.1093\/nar\/21.14.3197","article-title":"Antisense oligodeoxynucleotides: Synthesis, biophysical and biological evaluation of oligodeoxynucleotides containing modified pyrimidines","volume":"21","author":"Sanghvi","year":"1993","journal-title":"Nucleic Acids Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3513","DOI":"10.1073\/pnas.96.7.3513","article-title":"A cytosine analog that confers enhanced potency to antisense oligonucleotides","volume":"96","author":"Flanagan","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4503","DOI":"10.1021\/ol701826x","article-title":"Binding affinities of oligonucleotides and PNAs containing phenoxazine and G-clamp cytosine analogues are unusually sequence-dependent","volume":"9","author":"Ortega","year":"2007","journal-title":"Org. Lett."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Wang, T., Larcher, L.M., Ma, L., and Veedu, R.N. (2018). Systematic screening of commonly used commercial transfection reagents towards efficient transfection of single-stranded oligonucleotides. Molecules, 23.","DOI":"10.3390\/molecules23102564"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1002\/ehf2.13154","article-title":"Ligand conjugated antisense oligonucleotide for the treatment of transthyretin amyloidosis: Preclinical and phase 1 data","volume":"8","author":"Viney","year":"2021","journal-title":"ESC Heart Fail."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e136","DOI":"10.1016\/S2352-3026(18)30021-8","article-title":"Liposomal Grb2 antisense oligodeoxynucleotide (BP1001) in patients with refractory or relapsed haematological malignancies: A single-centre, open-label, dose-escalation, phase 1\/1b trial","volume":"5","author":"Ohanian","year":"2018","journal-title":"Lancet Haematol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.ymthe.2019.12.009","article-title":"Retroviral insertional mutagenesis in humans: Evidence for four genetic mechanisms promoting expansion of cell clones","volume":"28","author":"Bushman","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/j.ymthe.2021.03.010","article-title":"A pause in gene therapy: Reflecting on the unique challenges of sickle cell disease","volume":"29","author":"Leonard","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_106","unstructured":"Servick, K. (2022, July 15). Gene Therapy Clinical Trial Halted as Cancer Risk Surfaces. Available online: https:\/\/www.science.org\/content\/article\/gene-therapy-clinical-trial-halted-cancer-risk-surfaces."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e58","DOI":"10.1002\/cpmo.58","article-title":"Viral vectors for gene transfer","volume":"8","author":"Chen","year":"2018","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1038\/mt.2008.141","article-title":"The immunogenicity of adenovirus vectors limits the multispecificity of CD8 T-cell responses to vector-encoded transgenic antigens","volume":"16","author":"Schirmbeck","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/mt.2009.256","article-title":"Evidence for the failure of adeno-associated virus serotype 5 to package a viral genome \u22658.2 kb","volume":"18","author":"Lai","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Ricobaraza, A., Gonzalez-Aparicio, M., Mora-Jimenez, L., Lumbreras, S., and Hernandez-Alcoceba, R. (2020). High-capacity adenoviral vectors: Expanding the scope of gene therapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103643"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Gurumoorthy, N., Nordin, F., Tye, G.J., Wan Kamarul Zaman, W.S., and Ng, M.H. (2022). Non-Integrating Lentiviral Vectors in Clinical Applications: A Glance Through. Biomedicines, 10.","DOI":"10.3390\/biomedicines10010107"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1073\/pnas.92.4.1162","article-title":"Retrovirus-mediated transfer of an angiotensin type I receptor (AT1-R) antisense sequence decreases AT1-Rs and angiotensin II action in astroglial and neuronal cells in primary cultures from the brain","volume":"92","author":"Lu","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1161\/01.HYP.29.1.177","article-title":"Antisense inhibition and adeno-associated viral vector delivery for reducing hypertension","volume":"29","author":"Phillips","year":"1997","journal-title":"Hypertension"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Imbert, M., Dias-Florencio, G., and Goyenvalle, A. (2017). Viral vector-mediated antisense therapy for genetic diseases. Genes, 8.","DOI":"10.3390\/genes8020051"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Geib, T., and Hertel, K.J. (2009). Restoration of full-length SMN promoted by adenoviral vectors expressing RNA antisense oligonucleotides embedded in U7 snRNAs. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008204"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1038\/sj.mt.6300200","article-title":"Spinal muscular atrophy: SMN2 pre-mRNA splicing corrected by a U7 snRNA derivative carrying a splicing enhancer sequence","volume":"15","author":"Marquis","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1038\/mt.2012.26","article-title":"Engineering multiple U7snRNA constructs to induce single and multiexon-skipping for Duchenne muscular dystrophy","volume":"20","author":"Goyenvalle","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/0092-8674(88)90263-2","article-title":"Cellular uptake of the tat protein from human immunodeficiency virus","volume":"55","author":"Frankel","year":"1988","journal-title":"Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/0092-8674(88)90262-0","article-title":"Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein","volume":"55","author":"Green","year":"1988","journal-title":"Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3370","DOI":"10.1074\/jbc.M805550200","article-title":"Cell entry of arginine-rich peptides is independent of endocytosis","volume":"284","author":"Nowak","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"12416","DOI":"10.1021\/bi00164a017","article-title":"Interaction of antimicrobial dermaseptin and its fluorescently labeled analogs with phospholipid membranes","volume":"31","author":"Pouny","year":"1992","journal-title":"Biochemistry"},{"key":"ref_122","first-page":"575","article-title":"Cell-penetrating peptides: Achievements and challenges in application for cancer treatment","volume":"102","author":"Shin","year":"2014","journal-title":"J. Biomed. Mater. Res. Part A Off. J. Soc. Biomater. Jpn. Soc. Biomater. Aust. Soc. Biomater. Korean Soc. Biomater."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"8450","DOI":"10.1021\/bi960342a","article-title":"Transbilayer transport of ions and lipids coupled with mastoparan \u00d7 translocation","volume":"35","author":"Matsuzaki","year":"1996","journal-title":"Biochemistry"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/S0962-8924(98)80017-2","article-title":"Trojan peptides: The penetratin system for intracellular delivery","volume":"8","author":"Derossi","year":"1998","journal-title":"Trends Cell Biol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1111\/j.1582-4934.2007.00062.x","article-title":"Macropinocytosis: Searching for an endocytic identity and role in the uptake of cell penetrating peptides","volume":"11","author":"Jones","year":"2007","journal-title":"J. Cell. Mol. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1021\/acs.bioconjchem.6b00082","article-title":"Syndecan-4 is a receptor for clathrin-mediated endocytosis of arginine-rich cell-penetrating peptides","volume":"27","author":"Kawaguchi","year":"2016","journal-title":"Bioconjugate Chem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1007\/s11095-007-9303-7","article-title":"Cell penetrating peptides: Intracellular pathways and pharmaceutical perspectives","volume":"24","author":"Patel","year":"2007","journal-title":"Pharm. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1074\/jbc.M509813200","article-title":"Mechanism of uptake of C105Y; a novel cell-penetrating peptide","volume":"281","author":"Rhee","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1023\/A:1016260110049","article-title":"Improved cellular delivery of antisense oligonucleotides using transferrin receptor antibody-oligonucleotide conjugates","volume":"12","author":"Walker","year":"1995","journal-title":"Pharm. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.omtn.2018.04.004","article-title":"Antibody-antisense oligonucleotide conjugate downregulates a key gene in glioblastoma stem cells","volume":"11","author":"Arnold","year":"2018","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"632","DOI":"10.2119\/molmed.2015.00210","article-title":"Novel targeted therapy for Precursor B-Cell acute Lymphoblastic Leukemia: Anti-CD22 antibody-MXD3 antisense Oligonucleotide Conjugate","volume":"22","author":"Satake","year":"2016","journal-title":"Mol. Med."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Vorobyeva, M., Vorobjev, P., and Venyaminova, A. (2016). Multivalent aptamers: Versatile tools for diagnostic and therapeutic applications. Molecules, 21.","DOI":"10.3390\/molecules21121613"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.omtn.2020.11.016","article-title":"Base-modified aptamers obtained by cell-internalization SELEX facilitate cellular uptake of an antisense oligonucleotide","volume":"23","author":"Tanaka","year":"2021","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"8796","DOI":"10.1093\/nar\/gku531","article-title":"Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice","volume":"42","author":"Prakash","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.ymthe.2017.11.015","article-title":"Selective \u03b1-synuclein knockdown in monoamine neurons by intranasal oligonucleotide delivery: Potential therapy for Parkinson\u2019s disease","volume":"26","author":"Recasens","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.addr.2012.05.012","article-title":"Nanoparticle mediated non-covalent drug delivery","volume":"65","author":"Doane","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1021\/ja808137c","article-title":"Entrapment of hydrophobic drugs in nanoparticle monolayers with efficient release into cancer cells","volume":"131","author":"Kim","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"14489","DOI":"10.1021\/la202470k","article-title":"Enhanced drug loading on magnetic nanoparticles by layer-by-layer assembly using drug conjugates: Blood compatibility evaluation and targeted drug delivery in cancer cells","volume":"27","author":"Manju","year":"2011","journal-title":"Langmuir"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1021\/nn700408z","article-title":"Hydrogen-bonding layer-by-layer-assembled biodegradable polymeric micelles as drug delivery vehicles from surfaces","volume":"2","author":"Kim","year":"2008","journal-title":"ACS Nano"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"4116","DOI":"10.1021\/nl802098g","article-title":"Calcium phosphate nanocomposite particles for in vitro imaging and encapsulated chemotherapeutic drug delivery to cancer cells","volume":"8","author":"Kester","year":"2008","journal-title":"Nano Lett."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0169-409X(00)00116-2","article-title":"Nanoparticulate systems for the delivery of antisense oligonucleotides","volume":"47","author":"Lambert","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1021\/acs.molpharmaceut.0c01238","article-title":"Advances in the design of (nano) formulations for delivery of antisense oligonucleotides and small interfering RNA: Focus on the central nervous system","volume":"18","author":"Kont","year":"2021","journal-title":"Mol. Pharm."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"8173","DOI":"10.1002\/anie.201914751","article-title":"Systemic brain delivery of antisense oligonucleotides across the blood\u2013brain barrier with a glucose-coated polymeric nanocarrier","volume":"59","author":"Min","year":"2020","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jconrel.2006.04.014","article-title":"Toxicity of cationic lipids and cationic polymers in gene delivery","volume":"114","author":"Lv","year":"2006","journal-title":"J. Control. Release"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1021\/acs.molpharmaceut.8b01290","article-title":"Lipid nanoparticles for delivery of therapeutic RNA oligonucleotides","volume":"16","author":"Moss","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"23279","DOI":"10.1039\/C5RA26215A","article-title":"PEG\/heparin-decorated lipid\u2013polymer hybrid nanoparticles for long-circulating drug delivery","volume":"6","author":"Sheng","year":"2016","journal-title":"RSC Adv."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.2147\/DDDT.S246574","article-title":"Combination chemotherapy of lung cancer\u2013co-delivery of docetaxel prodrug and cisplatin using aptamer-decorated lipid\u2013polymer hybrid nanoparticles","volume":"14","author":"Wu","year":"2020","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11095-018-2566-3","article-title":"Application of a quality-by-design approach to optimise lipid-polymer hybrid nanoparticles loaded with a splice-correction antisense oligonucleotide: Maximising loading and intracellular delivery","volume":"36","author":"Thanki","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1080\/03639045.2016.1200069","article-title":"Co-delivery of pemetrexed and miR-21 antisense oligonucleotide by lipid-polymer hybrid nanoparticles and effects on glioblastoma cells","volume":"43","author":"Devrim","year":"2017","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"476","DOI":"10.3389\/fnins.2017.00476","article-title":"Improving the delivery of SOD1 antisense oligonucleotides to motor neurons using calcium phosphate-lipid nanoparticles","volume":"11","author":"Chen","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"9272","DOI":"10.1002\/anie.201602188","article-title":"Cell-penetrating poly (disulfide) assisted intracellular delivery of mesoporous silica nanoparticles for inhibition of miR-21 function and detection of subsequent therapeutic effects","volume":"55","author":"Yu","year":"2016","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"102127","DOI":"10.1016\/j.nano.2019.102127","article-title":"MXD3 antisense oligonucleotide with superparamagnetic iron oxide nanoparticles: A new targeted approach for neuroblastoma","volume":"24","author":"Yoshida","year":"2020","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"112167","DOI":"10.1016\/j.msec.2021.112167","article-title":"Delivery of antisense oligonucleotides using multi-layer coated gold nanoparticles to methicillin-resistant S. aureus for combinatorial treatment","volume":"126","author":"Beha","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1089\/nat.2013.0450","article-title":"Nanoparticle delivery of antisense oligonucleotides and their application in the exon skipping strategy for Duchenne muscular dystrophy","volume":"24","author":"Falzarano","year":"2014","journal-title":"Nucleic Acid Ther."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.cell.2016.01.043","article-title":"Communication by extracellular vesicles: Where we are and where we need to go","volume":"164","author":"Tkach","year":"2016","journal-title":"Cell"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Margolis, L., and Sadovsky, Y. (2019). The biology of extracellular vesicles: The known unknowns. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000363"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1038\/s41467-018-04791-8","article-title":"Efficient RNA drug delivery using red blood cell extracellular vesicles","volume":"9","author":"Usman","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.omtn.2021.12.029","article-title":"Glioma-targeted delivery of exosome-encapsulated antisense oligonucleotides using neural stem cells","volume":"27","author":"Adamus","year":"2022","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"105218","DOI":"10.1016\/j.nbd.2020.105218","article-title":"Exosome-mediated delivery of antisense oligonucleotides targeting \u03b1-synuclein ameliorates the pathology in a mouse model of Parkinson\u2019s disease","volume":"148","author":"Yang","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"e21557","DOI":"10.1096\/fj.202002777RR","article-title":"Therapeutic targeting of STAT3 with small interference RNAs and antisense oligonucleotides embedded exosomes in liver fibrosis","volume":"35","author":"Tang","year":"2021","journal-title":"FASEB J."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"eaat0195","DOI":"10.1126\/scitranslmed.aat0195","article-title":"Anchor peptide captures, targets, and loads exosomes of diverse origins for diagnostics and therapy","volume":"10","author":"Gao","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1038\/mt.2016.126","article-title":"Exosome-mediated delivery of hydrophobically modified siRNA for huntingtin mRNA silencing","volume":"24","author":"Didiot","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41556-018-0250-9","article-title":"Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication","volume":"21","author":"Mathieu","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1212\/WNL.0000000000000926","article-title":"CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS","volume":"83","author":"Limmroth","year":"2014","journal-title":"Neurology"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jneuroim.2004.10.029","article-title":"Antisense oligonucleotide blockade of alpha 4 integrin prevents and reverses clinical symptoms in murine experimental autoimmune encephalomyelitis","volume":"160","author":"Myers","year":"2005","journal-title":"J. Neuroimmunol."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Woodcock, I.R., Tachas, G., Desmin, N., Houweling, P.J., Yiu, E., Kean, M., Emmanuel, J., Kennedy, R., Carroll, K., and de Valle, K. (2022). A Phase 2 open-label study to determine the safety and efficacy of weekly dosing of ATL1102 in patients with non-ambulatory Duchenne muscular dystrophy. medRxiv.","DOI":"10.1101\/2022.01.16.22269029"},{"key":"ref_167","unstructured":"Astra Zeneca (2022, July 15). Eplontersen Met Co-Primary and Secondary Endpoints in Interim Analysis of the NEURO-TTRansform Phase III Trial for Hereditary Transthyretin-Mediated Amyloid Polyneuropathy (ATTRv-PN). Available online: https:\/\/www.astrazeneca.com\/media-centre\/press-releases\/2022\/eplontersen-phase-iii-trial-met-co-primary-endpoints.html."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1056\/NEJMoa1813279","article-title":"Patient-customized oligonucleotide therapy for a rare genetic disease","volume":"381","author":"Kim","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.exger.2010.08.026","article-title":"Intranasal insulin as a therapeutic option in the treatment of cognitive impairments","volume":"46","author":"Benedict","year":"2011","journal-title":"Exp. Gerontol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"717192","DOI":"10.3389\/fphar.2021.717192","article-title":"Current state and future directions of intranasal delivery route for central nervous system disorders: A scientometric and visualization analysis","volume":"12","author":"Wu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13287-021-02274-0","article-title":"Advances in intranasal application of stem cells in the treatment of central nervous system diseases","volume":"12","author":"Zhang","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1002\/jps.21924","article-title":"Intranasal delivery to the central nervous system: Mechanisms and experimental considerations","volume":"99","author":"Dhuria","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"10962","DOI":"10.1073\/pnas.1605731113","article-title":"Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy","volume":"113","author":"Hammond","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ejhg.2011.134","article-title":"Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: Clinical laboratory analysis of> 72 400 specimens","volume":"20","author":"Sugarman","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/ajmg.10425","article-title":"Genetic risk assessment in carrier testing for spinal muscular atrophy","volume":"110","author":"Ogino","year":"2002","journal-title":"Am. J. Med. Genet."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0960-8966(91)90039-U","article-title":"Population frequencies of inherited neuromuscular diseases\u2014A world survey","volume":"1","author":"Emery","year":"1991","journal-title":"Neuromuscul. Disord."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/S0387-7604(02)00103-1","article-title":"Oxidative stress and disturbed glutamate transport in spinal muscular atrophy","volume":"24","author":"Hayashi","year":"2002","journal-title":"Brain Dev."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"9920","DOI":"10.1073\/pnas.94.18.9920","article-title":"Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos","volume":"94","author":"Schrank","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"e174","DOI":"10.1038\/mtna.2014.23","article-title":"A short antisense oligonucleotide ameliorates symptoms of severe mouse models of spinal muscular atrophy","volume":"3","author":"Keil","year":"2014","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"11746","DOI":"10.1038\/srep11746","article-title":"Spinal muscular atrophy phenotype is ameliorated in human motor neurons by SMN increase via different novel RNA therapeutic approaches","volume":"5","author":"Nizzardo","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1056\/NEJMoa1710504","article-title":"Nusinersen versus sham control in later-onset spinal muscular atrophy","volume":"378","author":"Mercuri","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_182","first-page":"e413","article-title":"Nusinersen in adult patients with spinal muscular atrophy: Observations from a single center","volume":"95","author":"Visser","year":"2020","journal-title":"Neurology"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S1474-4422(20)30037-5","article-title":"Nusinersen in adults with 5q spinal muscular atrophy: A non-interventional, multicentre, observational cohort study","volume":"19","author":"Hagenacker","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1136\/jnnp-2020-323822","article-title":"Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3","volume":"91","author":"Maggi","year":"2020","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2147\/TCRM.S219979","article-title":"Diagnosis and treatment of hereditary transthyretin amyloidosis (hATTR) polyneuropathy: Current perspectives on improving patient care","volume":"16","author":"Luigetti","year":"2020","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1007\/s40265-018-0983-6","article-title":"Patisiran: First global approval","volume":"78","author":"Hoy","year":"2018","journal-title":"Drugs"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1007\/s40265-022-01765-5","article-title":"Vutrisiran: First Approval","volume":"82","author":"Keam","year":"2022","journal-title":"Drugs"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.nmd.2014.03.008","article-title":"A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy","volume":"24","author":"Mah","year":"2014","journal-title":"Neuromuscul. Disord."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13023-017-0631-3","article-title":"The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: An evidence review","volume":"12","author":"Ryder","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-021-00248-3","article-title":"Duchenne muscular dystrophy","volume":"7","author":"Duan","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1016\/S0140-6736(19)32910-1","article-title":"Muscular dystrophies","volume":"394","author":"Mercuri","year":"2019","journal-title":"Lancet"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1089\/hum.2012.234","article-title":"Clinical trials using antisense oligonucleotides in duchenne muscular dystrophy","volume":"24","author":"Koo","year":"2013","journal-title":"Hum. Gene Ther."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/humu.20918","article-title":"Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations","volume":"30","author":"Fokkema","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3233\/JND-170272","article-title":"Long-term pulmonary function in Duchenne muscular dystrophy: Comparison of eteplirsen-treated patients to natural history","volume":"5","author":"Kinane","year":"2018","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Brogna, C., Coratti, G., Pane, M., Ricotti, V., Messina, S., D\u2019Amico, A., Bruno, C., Vita, G., Berardinelli, A., and Mazzone, E. (2019). Long-term natural history data in Duchenne muscular dystrophy ambulant patients with mutations amenable to skip exons 44, 45, 51 and 53. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0220714"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"e2270","DOI":"10.1212\/WNL.0000000000009233","article-title":"Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy","volume":"94","author":"Frank","year":"2020","journal-title":"Neurology"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1002\/acn3.51235","article-title":"Viltolarsen in Japanese Duchenne muscular dystrophy patients: A phase 1\/2 study","volume":"7","author":"Komaki","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1001\/jamaneurol.2020.1264","article-title":"Safety, tolerability, and efficacy of viltolarsen in boys with duchenne muscular dystrophy amenable to exon 53 skipping: A phase 2 randomized clinical trial","volume":"77","author":"Clemens","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"493","DOI":"10.3233\/JND-220811","article-title":"Long-Term Functional Efficacy and Safety of Viltolarsen in Patients with Duchenne Muscular Dystrophy","volume":"9","author":"Clemens","year":"2022","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_200","unstructured":"USA FDA (2022, August 12). Amondys 45 (Casimersen) Injection, for Intravenous Use: US Prescribing Information 2021, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/213026lbl.pdf."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.addr.2015.03.008","article-title":"Antisense oligonucleotides in therapy for neurodegenerative disorders","volume":"87","author":"Evers","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1146\/annurev-neuro-070918-050501","article-title":"Antisense oligonucleotide therapies for neurodegenerative diseases","volume":"42","author":"Bennett","year":"2019","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1126\/science.aba4624","article-title":"Antisense oligonucleotides for neurodegeneration","volume":"367","author":"Leavitt","year":"2020","journal-title":"Science"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/brain\/awz328","article-title":"Antisense oligonucleotide therapeutics in neurodegenerative diseases: The case of polyglutamine disorders","volume":"143","author":"Silva","year":"2020","journal-title":"Brain"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1756286418776932","DOI":"10.1177\/1756286418776932","article-title":"Antisense oligonucleotides in neurological disorders","volume":"11","author":"Wurster","year":"2018","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1093\/brain\/awab423","article-title":"Antisense therapies in neurological diseases","volume":"145","author":"Durr","year":"2022","journal-title":"Brain"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1212\/WNL.49.4.1111","article-title":"VLA-4 expression on peripheral blood lymphocytes is downregulated after treatment of multiple sclerosis with interferon beta","volume":"49","author":"Calabresi","year":"1997","journal-title":"Neurology"},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"De Andr\u00e9s, C., Teijeiro, R., Alonso, B., S\u00e1nchez-Madrid, F., Mart\u00ednez, M.L., De Villoria, J.G., Fern\u00e1ndez-Cruz, E., and S\u00e1nchez-Ram\u00f3n, S. (2012). Long-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034103"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/intimm\/dxu096","article-title":"Therapeutic uses of anti-\u03b14-integrin (anti-VLA-4) antibodies in multiple sclerosis","volume":"27","author":"Schwab","year":"2015","journal-title":"Int. Immunol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1002\/(SICI)1097-4547(20000315)59:6<712::AID-JNR3>3.0.CO;2-L","article-title":"Treatment of experimental autoimmune encephalomyelitis with antisense oligonucleotides against the low affinity neurotrophin receptor","volume":"59","author":"Epa","year":"2000","journal-title":"J. Neurosci. Res."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"7768","DOI":"10.4049\/jimmunol.176.12.7768","article-title":"IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production","volume":"176","author":"Balashov","year":"2006","journal-title":"J. Immunol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/(SICI)1096-8628(19970905)71:4<475::AID-AJMG20>3.0.CO;2-C","article-title":"Leukodystrophy incidence in Germany","volume":"71","author":"Heim","year":"1997","journal-title":"Am. J. Med. Genet."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.spen.2012.10.001","article-title":"Relative incidence of inherited white matter disorders in childhood to acquired pediatric demyelinating disorders","volume":"19","author":"Vanderver","year":"2012","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1212\/WNL.0b013e3181eee46b","article-title":"The burden of inherited leukodystrophies in children","volume":"75","author":"Bonkowsky","year":"2010","journal-title":"Neurology"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.pediatrneurol.2020.06.005","article-title":"Elevated leukodystrophy incidence predicted from genomics databases","volume":"111","author":"Soderholm","year":"2020","journal-title":"Pediatr. Neurol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/ana.25118","article-title":"Antisense suppression of glial fibrillary acidic protein as a treatment for Alexander disease","volume":"83","author":"Hagemann","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41586-020-2494-3","article-title":"Suppression of proteolipid protein rescues Pelizaeus\u2013Merzbacher disease","volume":"585","author":"Elitt","year":"2020","journal-title":"Nature"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/ana.25674","article-title":"Antisense oligonucleotide reverses leukodystrophy in Canavan disease mice","volume":"87","author":"Hull","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/brain\/72.3.373","article-title":"Progressive fibrinoid degeneration of fibrillary astrocytes associated with mental retardation in a hydrocephalic infant","volume":"72","author":"Alexander","year":"1949","journal-title":"Brain"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1007\/s00415-011-6056-3","article-title":"Nationwide survey of Alexander disease in Japan and proposed new guidelines for diagnosis","volume":"258","author":"Yoshida","year":"2011","journal-title":"J. Neurol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1055\/s-2000-7479","article-title":"Alexander disease-classification revisited and isolation of a neonatal form","volume":"31","author":"Springer","year":"2000","journal-title":"Neuropediatrics"},{"key":"ref_222","unstructured":"Pagon, R.A., Adam, M.P., and Ardinger, H.H. (2022, September 16). Alexander disease, GeneReviews [Internet], Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1172."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1212\/WNL.0b013e3182309f72","article-title":"GFAP mutations, age at onset, and clinical subtypes in Alexander disease","volume":"77","author":"Prust","year":"2011","journal-title":"Neurology"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1016\/j.yexcr.2007.04.004","article-title":"GFAP and its role in Alexander disease","volume":"313","author":"Quinlan","year":"2007","journal-title":"Exp. Cell Res."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/ana.20406","article-title":"Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease","volume":"57","author":"Li","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0896-6273(95)90238-4","article-title":"Mice devoid of the glial fibrillary acidic protein develop normally and are susceptible to scrapie prions","volume":"14","author":"Gomi","year":"1995","journal-title":"Neuron"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"11162","DOI":"10.1523\/JNEUROSCI.3260-06.2006","article-title":"Alexander disease-associated glial fibrillary acidic protein mutations in mice induce Rosenthal fiber formation and a white matter stress response","volume":"26","author":"Hagemann","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"e00109","DOI":"10.1042\/AN20130003","article-title":"GFAP expression as an indicator of disease severity in mouse models of Alexander disease","volume":"5","author":"Jany","year":"2013","journal-title":"ASN Neuro"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"eabg4711","DOI":"10.1126\/scitranslmed.abg4711","article-title":"Antisense therapy in a rat model of Alexander disease reverses GFAP pathology, white matter deficits, and motor impairment","volume":"13","author":"Hagemann","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1001\/archneurpsyc.1928.02210180041003","article-title":"Progressive degenerative subcortical encephalopathy (Schilder\u2019s disease)","volume":"20","author":"Globus","year":"1928","journal-title":"Arch. Neurol. Psychiatry"},{"key":"ref_231","first-page":"1250","article-title":"Prevalence of Canavan disease heterozygotes in the New York metropolitan Ashkenazi Jewish population","volume":"57","author":"Kronn","year":"1995","journal-title":"Am. J. Hum. Genet."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1002\/ajmg.a.20334","article-title":"Canavan disease: Carrier-frequency determination in the Ashkenazi Jewish population and development of a novel molecular diagnostic assay","volume":"124","author":"Feigenbaum","year":"2004","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/pd.1943","article-title":"Carrier frequency of autosomal-recessive disorders in the Ashkenazi Jewish population: Should the rationale for mutation choice for screening be reevaluated?","volume":"28","author":"Fares","year":"2008","journal-title":"Prenat. Diagn."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1016\/j.drudis.2022.05.019","article-title":"The pathogenesis of, and pharmacological treatment for, Canavan disease","volume":"27","author":"Wei","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_235","unstructured":"Rosenberg, R.N., and Pascual, J.M. (2020). Canavan disease. Rosenberg\u2019s Molecular and Genetic Basis of Neurological and Psychiatric Disease, Academic Press. [6th ed.]."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/ana.26211","article-title":"Ablating the Transporter Sodium-Dependent Dicarboxylate Transporter 3 Prevents Leukodystrophy in Canavan Disease Mice","volume":"90","author":"Wang","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ijdevneu.2007.04.002","article-title":"N-acetylaspartic acid promotes oxidative stress in cerebral cortex of rats","volume":"25","author":"Pederzolli","year":"2007","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3109\/00207454.2011.558225","article-title":"Upregulation of N-acetylaspartic acid induces oxidative stress to contribute in disease pathophysiology","volume":"121","author":"Surendran","year":"2011","journal-title":"Int. J. Neurosci."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.ejpn.2009.11.006","article-title":"Lithium citrate reduces excessive intra-cerebral N-acetyl aspartate in Canavan disease","volume":"14","author":"Assadi","year":"2010","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1023\/A:1015504031229","article-title":"The effects of lithium chloride and other substances on levels of brain N-acetyl-L-aspartic acid in Canavan disease-like rats","volume":"27","author":"Baslow","year":"2002","journal-title":"Neurochem. Res."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/S0006-8993(00)02797-9","article-title":"Chronic lithium and sodium valproate both decrease the concentration of myo-inositol and increase the concentration of inositol monophosphates in rat brain","volume":"880","author":"Rotzinger","year":"2000","journal-title":"Brain Res."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1007\/s00415-014-7263-5","article-title":"Epidemiological, clinical, and genetic landscapes of hypomyelinating leukodystrophies","volume":"261","author":"Numata","year":"2014","journal-title":"J. Neurol."},{"key":"ref_243","first-page":"100","article-title":"\u00dcber eine eigenartige famili\u00e4re Entwicklungshemmung vornehmlich auf motorischem Gebiet","volume":"31","author":"Pelizaeus","year":"1899","journal-title":"Arch. F\u00fcr Psychiatr. Und Nervenkrankh."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF02893591","article-title":"Eine eigenartige famili\u00e4r-heredit\u00e4re Erkrankungsform (Aplasia axialis extracorticalis congenita)","volume":"3","author":"Merzbacher","year":"1910","journal-title":"Z. F\u00fcr Die Gesamte Neurol. Und Psychiatr."},{"key":"ref_245","unstructured":"Vinken, P., and Bruyn, G. (1996). Pelizaeus\u2013Merzbacher disease. Handbook of Clinical Neurology, Elsevier."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/B978-0-444-64076-5.00045-4","article-title":"Neurogenetics of Pelizaeus\u2013Merzbacher disease","volume":"148","author":"Goldman","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0896-6273(01)80046-5","article-title":"Assembly of CNS myelin in the absence of proteolipid protein","volume":"18","author":"Klugmann","year":"1997","journal-title":"Neuron"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/ana.10456","article-title":"A new leukoencephalopathy with brainstem and spinal cord involvement and high lactate","volume":"53","author":"Barkhof","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1136\/jmg.2009.068221","article-title":"DARS2 mutations in mitochondrial leucoencephalopathy and multiple sclerosis","volume":"47","author":"Isohanni","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"4181","DOI":"10.1093\/hmg\/ddx307","article-title":"DARS2 protects against neuroinflammation and apoptotic neuronal loss, but is dispensable for myelin producing cells","volume":"26","author":"Aradjanski","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s11689-019-9292-y","article-title":"Mitochondrial aminoacyl-tRNA synthetase disorders: An emerging group of developmental disorders of myelination","volume":"11","author":"Fine","year":"2019","journal-title":"J. Neurodev. Disord."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.omtn.2022.06.015","article-title":"Developing antisense oligonucleotides for a TECPR2 mutation-induced, ultra-rare neurological disorder using patient-derived cellular models","volume":"29","author":"Williams","year":"2022","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1089\/nat.2021.0039","article-title":"Preparing n-of-1 antisense oligonucleotide treatments for rare neurological diseases in Europe: Genetic, regulatory, and ethical perspectives","volume":"32","author":"Synofzik","year":"2022","journal-title":"Nucleic Acid Ther."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/j.1469-8749.1965.tb07844.x","article-title":"\u2018Puppet\u2019children a report on three cases","volume":"7","author":"Angelman","year":"1965","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/ajmg.a.31074","article-title":"Angelman syndrome 2005: Updated consensus for diagnostic criteria","volume":"140","author":"Williams","year":"2006","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s13311-015-0361-y","article-title":"Angelman syndrome","volume":"12","author":"Margolis","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1093\/hmg\/dds130","article-title":"Ube3a-ATS is an atypical RNA polymerase II transcript that represses the paternal expression of Ube3a","volume":"21","author":"Meng","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nature13975","article-title":"Towards a therapy for Angelman syndrome by targeting a long non-coding RNA","volume":"518","author":"Meng","year":"2015","journal-title":"Nature"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"e145991","DOI":"10.1172\/jci.insight.145991","article-title":"Antisense oligonucleotide treatment rescues UBE3A expression and multiple phenotypes of an Angelman syndrome mouse model","volume":"6","author":"Milazzo","year":"2021","journal-title":"JCI Insight"},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13229-019-0277-1","article-title":"Delayed loss of UBE3A reduces the expression of Angelman syndrome-associated phenotypes","volume":"10","author":"Sonzogni","year":"2019","journal-title":"Mol. Autism"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1111\/dmcn.14831","article-title":"UBE3A reinstatement as a disease-modifying therapy for Angelman syndrome","volume":"63","author":"Elgersma","year":"2021","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_262","first-page":"543","article-title":"Les epilepsies graves de l\u2019enfant","volume":"8","author":"Dravet","year":"1978","journal-title":"Vie Med."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1528-1167.2011.02994.x","article-title":"The core Dravet syndrome phenotype","volume":"52","author":"Dravet","year":"2011","journal-title":"Epilepsia"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1111\/j.1528-1167.2009.02179.x","article-title":"Stiripentol open study in Japanese patients with Dravet syndrome","volume":"50","author":"Inoue","year":"2009","journal-title":"Epilepsia"},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1001\/jamaneurol.2019.4113","article-title":"Fenfluramine for treatment-resistant seizures in patients with Dravet syndrome receiving stiripentol-inclusive regimens: A randomized clinical trial","volume":"77","author":"Nabbout","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1056\/NEJMoa1611618","article-title":"Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome","volume":"376","author":"Devinsky","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/j.1528-1167.2011.02997.x","article-title":"The genetics of Dravet syndrome","volume":"52","author":"Marini","year":"2011","journal-title":"Epilepsia"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"e152079","DOI":"10.1172\/JCI152079","article-title":"Antisense oligonucleotide therapy reduces seizures and extends life span in an SCN2A gain-of-function epilepsy model","volume":"131","author":"Li","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/ana.25676","article-title":"Scn8a antisense oligonucleotide is protective in mouse models of SCN8A encephalopathy and Dravet syndrome","volume":"87","author":"Lenk","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1124\/dmd.121.000418","article-title":"Adverse Drug Reactions and Toxicity of the Food and Drug Administration\u2013Approved Antisense Oligonucleotide Drugs","volume":"50","author":"Alhamadani","year":"2022","journal-title":"Drug Metab. Dispos."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1016\/S0196-9781(00)00339-9","article-title":"Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice","volume":"21","author":"Kumar","year":"2000","journal-title":"Peptides"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.brainres.2004.05.048","article-title":"Antisense directed at the A\u03b2 region of APP decreases brain oxidative markers in aged senescence accelerated mice","volume":"1018","author":"Poon","year":"2004","journal-title":"Brain Res."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.ymthe.2018.02.029","article-title":"Targeting amyloid-\u03b2 precursor protein, APP; splicing with antisense oligonucleotides reduces toxic amyloid-\u03b2 production","volume":"26","author":"Chang","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1172\/JCI96499","article-title":"PMP22 antisense oligonucleotides reverse Charcot-Marie-Tooth disease type 1A features in rodent models","volume":"128","author":"Zhao","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_275","doi-asserted-by":"crossref","unstructured":"Ansseau, E., Vanderplanck, C., Wauters, A., Harper, S.Q., Copp\u00e9e, F., and Belayew, A. (2017). Antisense oligonucleotides used to target the DUX4 mRNA as therapeutic approaches in faciosscapulohumeral muscular dystrophy (FSHD). Genes, 8.","DOI":"10.3390\/genes8030093"},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1038\/mt.2016.111","article-title":"Morpholino-mediated knockdown of DUX4 toward facioscapulohumeral muscular dystrophy therapeutics","volume":"24","author":"Chen","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-021-21021-w","article-title":"Short antisense oligonucleotides alleviate the pleiotropic toxicity of RNA harboring expanded CGG repeats","volume":"12","author":"Derbis","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1097\/j.pain.0000000000002154","article-title":"Intranasal delivery of an antisense oligonucleotide to the RNA-binding protein HuR relieves nerve injury-induced neuropathic pain","volume":"162","author":"Borgonetti","year":"2021","journal-title":"Pain"},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/s001090000104","article-title":"Antisense prevention of neuronal damages following head injury in mice","volume":"78","author":"Shohami","year":"2000","journal-title":"J. Mol. Med."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0304-3940(98)00268-7","article-title":"Chemokine inhibition in rat stab wound brain injury using antisense oligodeoxynucleotides","volume":"247","author":"Ghirnikar","year":"1998","journal-title":"Neurosci. Lett."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/jnc.13920","article-title":"Transient receptor potential vanilloid type 4 channels mediate Na-K-Cl-co-transporter-induced brain edema after traumatic brain injury","volume":"140","author":"Lu","year":"2017","journal-title":"J. Neurochem."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/11\/2389\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:11:11Z","timestamp":1760145071000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/11\/2389"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,5]]},"references-count":281,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["pharmaceutics14112389"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14112389","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,5]]}}}