{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T16:43:19Z","timestamp":1774543399877,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"national funds through FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["2019DGH1656"],"award-info":[{"award-number":["2019DGH1656"]}]},{"name":"national funds through FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["2019DGH1629"],"award-info":[{"award-number":["2019DGH1629"]}]},{"name":"national funds through FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDB\/00211\/2020"],"award-info":[{"award-number":["UIDB\/00211\/2020"]}]},{"name":"national funds through FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"Sanfilippo Children\u2019s Foundation","award":["2019DGH1656"],"award-info":[{"award-number":["2019DGH1656"]}]},{"name":"Sanfilippo Children\u2019s Foundation","award":["2019DGH1629"],"award-info":[{"award-number":["2019DGH1629"]}]},{"name":"Sanfilippo Children\u2019s Foundation","award":["UIDB\/00211\/2020"],"award-info":[{"award-number":["UIDB\/00211\/2020"]}]},{"name":"Sanfilippo Children\u2019s Foundation","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"SPDM","award":["2019DGH1656"],"award-info":[{"award-number":["2019DGH1656"]}]},{"name":"SPDM","award":["2019DGH1629"],"award-info":[{"award-number":["2019DGH1629"]}]},{"name":"SPDM","award":["UIDB\/00211\/2020"],"award-info":[{"award-number":["UIDB\/00211\/2020"]}]},{"name":"SPDM","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"CECA","award":["2019DGH1656"],"award-info":[{"award-number":["2019DGH1656"]}]},{"name":"CECA","award":["2019DGH1629"],"award-info":[{"award-number":["2019DGH1629"]}]},{"name":"CECA","award":["UIDB\/00211\/2020"],"award-info":[{"award-number":["UIDB\/00211\/2020"]}]},{"name":"CECA","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"AL4AnimalS","award":["2019DGH1656"],"award-info":[{"award-number":["2019DGH1656"]}]},{"name":"AL4AnimalS","award":["2019DGH1629"],"award-info":[{"award-number":["2019DGH1629"]}]},{"name":"AL4AnimalS","award":["UIDB\/00211\/2020"],"award-info":[{"award-number":["UIDB\/00211\/2020"]}]},{"name":"AL4AnimalS","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mucopolysaccharidosis type IIIC is a neurodegenerative lysosomal storage disorder (LSD) characterized by the accumulation of undegraded heparan sulfate (HS) due to the lack of an enzyme responsible for its degradation: acetyl-CoA:\u03b1-glucosaminide N-acetyltransferase (HGSNAT). Classical treatments are ineffective. Here, we attempt a new approach in genetic medicine, genetic substrate reduction therapy (gSRT), to counteract this neurological disorder. Briefly, we used synthetic oligonucleotides, particularly gapmer antisense oligonucleotides (ASOs), to target the synthesis of the accumulated compounds at the molecular level, downregulating a specific gene involved in the first step of HS biosynthesis, XYLT1. Our goal was to reduce HS production and, consequently, its accumulation. Initially, five gapmer ASOs were designed and their potential to decrease XYLT1 mRNA levels were tested in patient-derived fibroblasts. Subsequent analyses focused on the two best performing molecules alone. The results showed a high inhibition of the XYLT1 gene mRNA (around 90%), a decrease in xylosyltransferase I (XT-I) protein levels and a reduction in HS storage 6 and 10 days after transfection (up to 21% and 32%, respectively). Overall, our results are highly promising and may represent the initial step towards the development of a potential therapeutic option not only for MPS IIIC, but virtually for every other MPS III form. Ultimately, the same principle may also apply to other neuropathic MPS.<\/jats:p>","DOI":"10.3390\/ijms26031273","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T04:36:51Z","timestamp":1738557411000},"page":"1273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["mRNA Degradation as a Therapeutic Solution for Mucopolysaccharidosis Type IIIC: Use of Antisense Oligonucleotides to Promote Downregulation of Heparan Sulfate Synthesis"],"prefix":"10.3390","volume":"26","author":[{"given":"Juliana In\u00eas","family":"Santos","sequence":"first","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"},{"name":"Biology Department, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3111-4612","authenticated-orcid":false,"given":"Mariana","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"},{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences, CITAB, Inov4Agro, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6079-4780","authenticated-orcid":false,"given":"Matilde Barbosa","family":"Almeida","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"},{"name":"Department of Medical Sciences, Campus Universit\u00e1rio de Santiago, Edif\u00edcio da Sa\u00fade, Agra do Crasto, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5447-615X","authenticated-orcid":false,"given":"Hugo","family":"Rocha","sequence":"additional","affiliation":[{"name":"Newborn Screening, Metabolism and Genetics Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6005-7322","authenticated-orcid":false,"given":"Ana Joana","family":"Duarte","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"},{"name":"School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Liliana","family":"Matos","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"}]},{"given":"Luciana Vaz","family":"Moreira","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3726-2851","authenticated-orcid":false,"given":"Marisa","family":"Encarna\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4255-0946","authenticated-orcid":false,"given":"Paulo","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Newborn Screening, Metabolism and Genetics Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-1028","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Prata","sequence":"additional","affiliation":[{"name":"Biology Department, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal"},{"name":"Health Research and Innovation Institute, University of Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2222-3622","authenticated-orcid":false,"given":"Maria Francisca","family":"Coutinho","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8881-9197","authenticated-orcid":false,"given":"Sandra","family":"Alves","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,1]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s43856-023-00419-1","article-title":"Possibilities and limitations of antisense oligonucleotide therapies for the treatment of monogenic disorders","volume":"4","author":"Lauffer","year":"2024","journal-title":"Commun. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115283","DOI":"10.1016\/j.addr.2024.115283","article-title":"RNA therapies for CNS diseases","volume":"208","author":"Chua","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/s41573-020-0075-7","article-title":"Advances in oligonucleotide drug delivery","volume":"19","author":"Roberts","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e13243","DOI":"10.15252\/emmm.202013243","article-title":"Delivery of oligonucleotide-based therapeutics: Challenges and opportunities","volume":"13","author":"Hammond","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.nmd.2017.05.011","article-title":"Spinal muscular atrophy: A changing phenotype beyond the clinical trials","volume":"27","author":"Tizzano","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.nmd.2019.09.007","article-title":"Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study","volume":"29","author":"Bertini","year":"2019","journal-title":"Neuromuscul. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s40265-023-01904-6","article-title":"Tofersen: First Approval","volume":"83","author":"Blair","year":"2023","journal-title":"Drugs"},{"key":"ref_9","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_10","doi-asserted-by":"crossref","unstructured":"Amanat, M., Nemeth, C.L., Fine, A.S., Leung, D.G., and Fatemi, A. (2022). Antisense Oligonucleotide Therapy for the Nervous System: From Bench to Bedside with Emphasis on Pediatric Neurology. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14112389"},{"key":"ref_11","unstructured":"Neufeld, E.F., and Muenzer, J. (2001). The Mucopolysaccharidoses. The Metabolic Basis of Inherited Disease, McGraw-Hill. [8th ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"v4","DOI":"10.1093\/rheumatology\/ker394","article-title":"Overview of the mucopolysaccharidoses","volume":"50","author":"Muenzer","year":"2011","journal-title":"Rheumatology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Coutinho, M.F., Lacerda, L., and Alves, S. (2012). Glycosaminoglycan storage disorders: A review. Biochem. Res. Int., 2012.","DOI":"10.1155\/2012\/471325"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.pedneo.2022.10.001","article-title":"Current and new therapies for mucopolysaccharidoses","volume":"64","author":"Blair","year":"2023","journal-title":"Pediatr. Neonatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41572-018-0025-4","article-title":"Lysosomal storage diseases","volume":"4","author":"Platt","year":"2018","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Coutinho, M.F., Santos, J.I., Matos, L., and Alves, S. (2016). Genetic Substrate Reduction Therapy: A Promising Approach for Lysosomal Storage Disorders. Diseases, 4.","DOI":"10.3390\/diseases4040033"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.curtheres.2008.04.002","article-title":"Genistin-rich soy isoflavone extract in substrate reduction therapy for Sanfilippo syndrome: An open-label, pilot study in 10 pediatric patients","volume":"69","author":"Piotrowska","year":"2008","journal-title":"Curr. Ther. Res. Clin. Exp."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1203\/01.pdr.0000233037.00707.da","article-title":"Inhibition of glycosaminoglycan synthesis using rhodamine B in a mouse model of mucopolysaccharidosis type IIIA","volume":"60","author":"Roberts","year":"2006","journal-title":"Pediatr. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/jimd.12316","article-title":"Novel therapies for mucopolysaccharidosis type III","volume":"44","author":"Davison","year":"2021","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.ymgme.2013.06.012","article-title":"High dose genistein aglycone therapy is safe in patients with mucopolysaccharidoses involving the central nervous system","volume":"109","author":"Kim","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1002\/jimd.12407","article-title":"High dose genistein in Sanfilippo syndrome: A randomised controlled trial","volume":"44","author":"Ghosh","year":"2021","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Derrick-Roberts, A.L.K., Jackson, M.R., Pyragius, C.E., and Byers, S. (2017). Substrate Deprivation Therapy to Reduce Glycosaminoglycan Synthesis Improves Aspects of Neurological and Skeletal Pathology in MPS I Mice. Diseases, 5.","DOI":"10.3390\/diseases5010005"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"603","DOI":"10.3109\/15563658708992660","article-title":"Acute exposure to rhodamine B","volume":"25","author":"Dire","year":"1987","journal-title":"J. Toxicol. Clin. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/ejhg.2009.143","article-title":"Gene silencing of EXTL2 and EXTL3 as a substrate deprivation therapy for heparan sulfate storing mucopolysaccharidoses","volume":"18","author":"Kaidonis","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Canals, I., Benet\u00f3, N., Cozar, M., Vilageliu, L., and Grinberg, D. (2015). EXTL2 and EXTL3 inhibition with siRNAs as a promising substrate reduction therapy for Sanfilippo C syndrome. Sci. Rep., 5.","DOI":"10.1038\/srep13654"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10953","DOI":"10.1074\/jbc.R112.437038","article-title":"Human genetic disorders caused by mutations in genes encoding biosynthetic enzymes for sulfated glycosaminoglycans","volume":"288","author":"Mizumoto","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/ejhg.2009.144","article-title":"Impairment of glycosaminoglycan synthesis in mucopolysaccharidosis type IIIA cells by using siRNA: A potential therapeutic approach for Sanfilippo disease","volume":"18","author":"Dziedzic","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"293","DOI":"10.18388\/abp.2012_2154","article-title":"Simultaneous siRNA-mediated silencing of pairs of genes coding for enzymes involved in glycosaminoglycan synthesis","volume":"59","author":"Dziedzic","year":"2012","journal-title":"Acta. Biochim. Pol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.ajhg.2014.01.020","article-title":"XYLT1 mutations in Desbuquois dysplasia type 2","volume":"94","author":"Bui","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/jhg.2016.30","article-title":"Exome sequencing reveals two novel compound heterozygous XYLT1 mutations in a Polish patient with Desbuquois dysplasia type 2 and growth hormone deficiency","volume":"61","author":"Jamsheer","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/jhg.2016.143","article-title":"Novel and recurrent XYLT1 mutations in two Turkish families with Desbuquois dysplasia, type 2","volume":"62","author":"Guo","year":"2017","journal-title":"J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ajhg.2018.11.005","article-title":"GGC Repeat Expansion and Exon 1 Methylation of XYLT1 Is a Common Pathogenic Variant in Baratela-Scott Syndrome","volume":"104","author":"LaCroix","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41419-023-05875-0","article-title":"Xylosyltransferase I mediates the synthesis of proteoglycans with long glycosaminoglycan chains and controls chondrocyte hypertrophy and collagen fibers organization of in the growth plate","volume":"14","author":"Taieb","year":"2023","journal-title":"Cell Death. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.ajhg.2015.04.017","article-title":"Homozygosity for frameshift mutations in XYLT2 result in a spondylo-ocular syndrome with bone fragility, cataracts, and hearing defects","volume":"96","author":"Munns","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.bbrc.2009.11.121","article-title":"Differences in gene expression of human xylosyltransferases and determination of acceptor specificities for various proteoglycans","volume":"391","author":"Roch","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Huang, Y.F., Mizumoto, S., and Fujita, M. (2021). Novel Insight Into Glycosaminoglycan Biosynthesis Based on Gene Expression Profiles. Front. Cell. Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.709018"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9416","DOI":"10.1073\/pnas.0700908104","article-title":"Polycystic disease caused by deficiency in xylosyltransferase 2, an initiating enzyme of glycosaminoglycan biosynthesis","volume":"104","author":"Condac","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ydbio.2013.10.014","article-title":"Forward genetics defines XYLT1 as a key, conserved regulator of early chondrocyte maturation and skeletal length","volume":"385","author":"Mis","year":"2014","journal-title":"Dev. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1055\/s-0042-118706","article-title":"Abnormal Proteoglycan Synthesis Due to Gene Defects Causes Skeletal Diseases with Overlapping Phenotypes","volume":"48","author":"Taylan","year":"2016","journal-title":"Horm. Metab. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1038\/s41366-019-0324-1","article-title":"Adipose tissue loss and lipodystrophy in xylosyltransferase II deficient mice","volume":"43","author":"Sivasami","year":"2019","journal-title":"Int. J. Obes."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kleine, A., K\u00fchle, M., Ly, T.D., Schmidt, V., Faust-Hinse, I., Knabbe, C., and Fischer, B. (2024). Xylosyltransferase-Deficiency in Human Dermal Fibroblasts Induces Compensatory Myofibroblast Differentiation and Long-Term ECM Reduction. Biomedicines, 12.","DOI":"10.3390\/biomedicines12030572"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1093\/nar\/gkad067","article-title":"Chemistry, structure and function of approved oligonucleotide therapeutics","volume":"51","author":"Egli","year":"2023","journal-title":"Nucleic. Acids. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s40259-024-00665-2","article-title":"Mechanisms of Action of the US Food and Drug Administration-Approved Antisense Oligonucleotide Drugs","volume":"38","author":"Sang","year":"2024","journal-title":"BioDrugs"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"102237","DOI":"10.1016\/j.omtn.2024.102237","article-title":"Strategies to improve the design of gapmer antisense oligonucleotide on allele-specific silencing","volume":"35","author":"Aguti","year":"2024","journal-title":"Mol. Ther. Nucleic. Acids."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1212\/WNL.0000000000002445","article-title":"Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy","volume":"86","author":"Chiriboga","year":"2016","journal-title":"Neurology"},{"key":"ref_46","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_47","doi-asserted-by":"crossref","unstructured":"McDowall, S., Aung-Htut, M., Wilton, S., and Li, D. (2024). Antisense oligonucleotides and their applications in rare neurological diseases. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1414658"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e186116","DOI":"10.1172\/JCI186116","article-title":"The expanding application of antisense oligonucleotides to neurodegenerative diseases","volume":"134","author":"Sumner","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.cca.2018.11.001","article-title":"LC-MS\/MS method for simultaneous quantification of heparan sulfate and dermatan sulfate in urine by butanolysis derivatization","volume":"488","author":"Forni","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Carvalho, S., Santos, J.I., Moreira, L., Gon\u00e7alves, M., David, H., Matos, L., Encarna\u00e7\u00e3o, M., Alves, S., and Coutinho, M.F. (2023). Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses. Biomedicines, 11.","DOI":"10.20944\/preprints202303.0552.v1"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1273\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:25:19Z","timestamp":1760027119000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,1]]},"references-count":50,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26031273"],"URL":"https:\/\/doi.org\/10.3390\/ijms26031273","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,1]]}}}