{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:31:55Z","timestamp":1790803915596,"version":"4.1.0"},"reference-count":106,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T00:00:00Z","timestamp":1658620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["22ae0201004h0005"],"award-info":[{"award-number":["22ae0201004h0005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["22K07927"],"award-info":[{"award-number":["22K07927"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["19K07952"],"award-info":[{"award-number":["19K07952"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT","doi-asserted-by":"publisher","award":["22ae0201004h0005"],"award-info":[{"award-number":["22ae0201004h0005"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT","doi-asserted-by":"publisher","award":["22K07927"],"award-info":[{"award-number":["22K07927"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT","doi-asserted-by":"publisher","award":["19K07952"],"award-info":[{"award-number":["19K07952"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sulfatases are enzymes that catalyze the removal of sulfate from biological substances, an essential process for the homeostasis of the body. They are commonly activated by the unusual amino acid formylglycine, which is formed from cysteine at the catalytic center, mediated by a formylglycine-generating enzyme as a post-translational modification. Sulfatases are expressed in various cellular compartments such as the lysosome, the endoplasmic reticulum, and the Golgi apparatus. The substrates of mammalian sulfatases are sulfolipids, glycosaminoglycans, and steroid hormones. These enzymes maintain neuronal function in both the central and the peripheral nervous system, chondrogenesis and cartilage in the connective tissue, detoxification from xenobiotics and pharmacological compounds in the liver, steroid hormone inactivation in the placenta, and the proper regulation of skin humidification. Human sulfatases comprise 17 genes, 10 of which are involved in congenital disorders, including lysosomal storage disorders, while the function of the remaining seven is still unclear. As for the genes responsible for pathogenesis, therapeutic strategies have been developed. Enzyme replacement therapy with recombinant enzyme agents and gene therapy with therapeutic transgenes delivered by viral vectors are administered to patients. In this review, the biochemical substrates, disease manifestation, and therapy for sulfatases are summarized.<\/jats:p>","DOI":"10.3390\/ijms23158153","type":"journal-article","created":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T22:49:02Z","timestamp":1658702942000},"page":"8153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy"],"prefix":"10.3390","volume":"23","author":[{"given":"Ryuichi","family":"Mashima","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahito","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"TOKIWA-Bio Inc., 2-1-6 Sengen, Tsukuba 305-0047, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"866196","DOI":"10.3389\/fmolb.2022.866196","article-title":"Sulfation Pathways During Neurodevelopment","volume":"9","author":"Clarke","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Barbeyron, T., Brillet-Gu\u00e9guen, L., Carr\u00e9, W., Carri\u00e8re, C., Caron, C., Czjzek, M., Hoebeke, M., and Michel, G. (2016). Matching the Diversity of Sulfated Biomolecules: Creation of a Classification Database for Sulfatases Reflecting Their Substrate Specificity. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164846"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"837636","DOI":"10.3389\/fpls.2022.837636","article-title":"Sulfatases: Critical Enzymes for Algal Polysaccharide Processing","volume":"13","author":"Hettle","year":"2022","journal-title":"Front. Plant Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.1172\/JCI28873","article-title":"Gene Therapy of Metachromatic Leukodystrophy Reverses Neurological Damage and Deficits in Mice","volume":"116","author":"Biffi","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/hmg\/ddaa006","article-title":"Enzyme Replacement Therapy in Mice Lacking Arylsulfatase B Targets Bone-Remodeling Cells, but not Chondrocytes","volume":"29","author":"Hendrickx","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10310","DOI":"10.1073\/pnas.1202071109","article-title":"Arylsulfatase G Inactivation Causes Loss of Heparan Sulfate 3-O-Sulfatase Activity and Mucopolysaccharidosis in Mice","volume":"109","author":"Kowalewski","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.1042\/BCJ20200546","article-title":"Arylsulfatase K Inactivation Causes Mucopolysaccharidosis Due to Deficient Glucuronate Desulfation of Heparan and Chondroitin Sulfate","volume":"477","author":"Trabszo","year":"2020","journal-title":"Biochem. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.1093\/hmg\/ddi364","article-title":"Development of MPS IVA Mouse (Galnstm(hC79S.mC76S)slu) Tolerant to Human N-Acetylgalactosamine-6-Sulfate Sulfatase","volume":"14","author":"Tomatsu","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1093\/hmg\/ddx058","article-title":"Disease Correction by AAV-Mediated Gene Therapy in a New Mouse Model of Mucopolysaccharidosis Type IIID","volume":"26","author":"Roca","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1089\/hum.2015.170","article-title":"A Preclinical Study Evaluating AAVrh10-Based Gene Therapy for Sanfilippo Syndrome","volume":"27","author":"Winner","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1007\/s10545-007-0641-8","article-title":"The Characterization of a Murine Model of Mucopolysaccharidosis II (Hunter Syndrome)","volume":"30","author":"Garcia","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Holst, C.R., Bou-Reslan, H., Gore, B.B., Wong, K., Grant, D., Chalasani, S., Carano, R.A., Frantz, G.D., Tessier-Lavigne, M., and Bolon, B. (2007). Secreted Sulfatases Sulf1 and Sulf2 Have Overlapping Yet Essential Roles in Mouse Neonatal Survival. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000575"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14900","DOI":"10.1074\/jbc.M413383200","article-title":"Molecular Characterization of the Human Calpha-Formylglycine-Generating Enzyme","volume":"280","author":"Mariappan","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5370","DOI":"10.1073\/pnas.1818274116","article-title":"Formylglycine-Generating Enzyme Binds Substrate Directly at a Mononuclear Cu(I) Center to Initiate O2 Activation","volume":"116","author":"Appel","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0092-8674(03)00347-7","article-title":"Multiple Sulfatase Deficiency Is Caused by Mutations in the Gene Encoding the Human C(Alpha)-Formylglycine Generating Enzyme","volume":"113","author":"Dierks","year":"2003","journal-title":"Cell"},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"1233158","DOI":"10.1126\/science.1233158","article-title":"Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy","volume":"341","author":"Biffi","year":"2013","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/ajmg.a.10950","article-title":"X-Linked Recessive Chondrodysplasia Punctata: Spectrum of Arylsulfatase E Gene Mutations and Expanded Clinical Variability","volume":"117A","author":"Andreucci","year":"2003","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1210\/er.2004-0003","article-title":"Steroid Sulfatase: Molecular Biology, Regulation, and Inhibition","volume":"26","author":"Reed","year":"2005","journal-title":"Endocr. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20867","DOI":"10.1038\/s41598-021-00051-w","article-title":"Steroid Sulfatase Deficiency Causes Cellular Senescence and Abnormal Differentiation by Inducing Yippee-Like 3 Expression in Human Keratinocytes","volume":"11","author":"Baek","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_21","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. Prim."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.gim.2022.04.002","article-title":"Long-Term Open-Label Phase I\/II Extension Study of Intrathecal Idursulfase-IT in the Treatment of Neuronopathic Mucopolysaccharidosis II","volume":"24","author":"Muenzer","year":"2022","journal-title":"Genet. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/j.ymthe.2018.02.032","article-title":"A Blood-Brain-Barrier-Penetrating Anti-Human Transferrin Receptor Antibody Fusion Protein for Neuronopathic Mucopolysaccharidosis II","volume":"26","author":"Sonoda","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e145445","DOI":"10.1172\/jci.insight.145445","article-title":"Iduronate-2-Sulfatase Transport Vehicle Rescues Behavioral and Skeletal Phenotypes in a Mouse Model of Hunter Syndrome","volume":"6","author":"Arguello","year":"2021","journal-title":"JCI Insight"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1089\/hum.2015.025","article-title":"Adeno-Associated Virus at 50: A golden Anniversary of Discovery, Research, and Gene Therapy Success\u2014A Personal Perspective","volume":"26","author":"Hastie","year":"2015","journal-title":"Hum. Gene Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7827","DOI":"10.1073\/pnas.0802866105","article-title":"Next Generation of Adeno-Associated Virus 2 Vectors: Point Mutations in Tyrosines Lead to High-Efficiency Transduction at Lower Doses","volume":"105","author":"Zhong","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1089\/hum.2020.269","article-title":"Safety of Direct Intraparenchymal AAVrh.10-Mediated Central Nervous System Gene Therapy for Metachromatic Leukodystrophy","volume":"32","author":"Rosenberg","year":"2021","journal-title":"Hum. Gene Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41576-020-00298-5","article-title":"Gene Therapy Using Haematopoietic Stem and Progenitor Cells","volume":"22","author":"Ferrari","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.omtm.2021.11.007","article-title":"Promoter Considerations in the Design of Lentiviral Vectors for Use in Treating Lysosomal Storage Diseases","volume":"24","author":"Rintz","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41436-020-01017-5","article-title":"Toward Newborn Screening of Metachromatic Leukodystrophy: Results from Analysis of over 27,000 Newborn Dried Blood Spots","volume":"23","author":"Hong","year":"2021","journal-title":"Genet. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6341","DOI":"10.1021\/acs.analchem.9b05274","article-title":"Leukocyte and Dried Blood Spot Arylsulfatase a Assay by Tandem Mass Spectrometry","volume":"92","author":"Hong","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/S0140-6736(16)30374-9","article-title":"Lentiviral Haemopoietic Stem-Cell Gene Therapy in Early-Onset Metachromatic Leukodystrophy: An Ad-Hoc Analysis of a Non-Randomised, Open-Label, Phase 1\/2 Trial","volume":"388","author":"Sessa","year":"2016","journal-title":"Lancet (Lond. Engl.)"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/S0140-6736(21)02017-1","article-title":"Lentiviral Haematopoietic Stem-Cell Gene Therapy for Early-Onset Metachromatic Leukodystrophy: Long-Term Results from a Non-Randomised, Open-Label, Phase 1\/2 Trial and Expanded Access","volume":"399","author":"Fumagalli","year":"2022","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.cell.2005.03.001","article-title":"Molecular Basis for Multiple Sulfatase Deficiency and Mechanism for Formylglycine Generation of the Human Formylglycine-Generating Enzyme","volume":"121","author":"Dierks","year":"2005","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1089\/hum.2018.189","article-title":"An Improved Adeno-Associated Virus Vector for Neurological Correction of the Mouse Model of Mucopolysaccharidosis IIIA","volume":"30","author":"Gray","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/sj.mt.6300012","article-title":"AAV1 Mediated Co-Expression of Formylglycine-Generating Enzyme and Arylsulfatase a Efficiently Corrects Sulfatide Storage in a Mouse Model of Metachromatic Leukodystrophy","volume":"15","author":"Kurai","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/hmg\/ddi425","article-title":"Intracerebral Adeno-Associated Virus-Mediated Gene Transfer in Rapidly Progressive Forms of Metachromatic Leukodystrophy","volume":"15","author":"Sevin","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1002\/jgm.1325","article-title":"Global Diffuse Distribution in the Brain and Efficient Gene Delivery to the Dorsal Root Ganglia by Intrathecal Injection of Adeno-Associated Viral Vector Serotype 1","volume":"11","author":"Iwamoto","year":"2009","journal-title":"J. Gene Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1089\/hum.2012.015","article-title":"Correction of Brain Oligodendrocytes by AAVrh.10 Intracerebral Gene Therapy in Metachromatic Leukodystrophy Mice","volume":"23","author":"Piguet","year":"2012","journal-title":"Hum. Gene Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1089\/humc.2013.239","article-title":"Comparative Efficacy and Safety of Multiple Routes of Direct CNS Administration of Adeno-Associated Virus Gene Transfer Vector Serotype rh.10 Expressing the Human Arylsulfatase A cDNA to Nonhuman Primates","volume":"25","author":"Rosenberg","year":"2014","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/gt.2014.17","article-title":"Long-Term Correction of Biochemical and Neurological Abnormalities in MLD Mice Model by Neonatal Systemic Injection of an AAV Serotype 9 vector","volume":"21","author":"Miyake","year":"2014","journal-title":"Gene Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13104","DOI":"10.1038\/srep13104","article-title":"Enzyme Replacement in the CSF to Treat Metachromatic Leukodystrophy in Mouse Model Using Single Intracerebroventricular Injection of Self-Complementary AAV1 Vector","volume":"5","author":"Hironaka","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"677895","DOI":"10.3389\/fnmol.2021.677895","article-title":"Complete Correction of Brain and Spinal Cord Pathology in Metachromatic Leukodystrophy Mice","volume":"14","author":"Audouard","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"20513","DOI":"10.1038\/s41598-021-99979-2","article-title":"Treatment of Adult Metachromatic Leukodystrophy Model Mice Using Intrathecal Administration of Type 9 AAV Vector Encoding Arylsulfatase A","volume":"11","author":"Miyake","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1089\/humc.2014.139","article-title":"Intracerebral Gene Therapy Using AAVrh.10-hARSA Recombinant Vector to Treat Patients with Early-Onset Forms of Metachromatic Leukodystrophy: Preclinical Feasibility and Safety Assessments in Nonhuman Primates","volume":"26","author":"Zerah","year":"2015","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/85454","article-title":"In Vivo Gene Therapy Of Metachromatic Leukodystrophy by Lentiviral Vectors: Correction of Neuropathology and Protection Against Learning Impairments in Affected Mice","volume":"7","author":"Consiglio","year":"2001","journal-title":"Nat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.ymthe.2005.06.438","article-title":"Axons Mediate the Distribution of Arylsulfatase a Within the Mouse Hippocampus Upon Gene Delivery","volume":"12","author":"Luca","year":"2005","journal-title":"Mol. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1089\/hum.2007.048","article-title":"Safety of arylsulfatase A Overexpression for Gene Therapy of Metachromatic Leukodystrophy","volume":"18","author":"Capotondo","year":"2007","journal-title":"Hum. Gene Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1093\/hmg\/ddq099","article-title":"Widespread Enzymatic Correction of CNS Tissues by a Single Intracerebral Injection of Therapeutic Lentiviral Vector in Leukodystrophy Mouse Models","volume":"19","author":"Lattanzi","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e187","DOI":"10.1038\/mtna.2014.39","article-title":"Lentivector Integration Sites in Ependymal Cells from a Model of Metachromatic Leukodystrophy: Non-B DNA as a New Factor Influencing Integration","volume":"3","author":"McAllister","year":"2014","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1089\/hum.2013.213","article-title":"Similar Therapeutic Efficacy between a single Administration of Gene Therapy and Multiple Administrations of Recombinant Enzyme in a Mouse Model of Lysosomal Storage Disease","volume":"25","author":"Ferla","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1038\/mt.2016.181","article-title":"Low-Dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease","volume":"24","author":"Alliegro","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.omtm.2017.07.004","article-title":"Non-Clinical Safety and Efficacy of an AAV2\/8 Vector Administered Intravenously for Treatment of Mucopolysaccharidosis Type VI","volume":"6","author":"Ferla","year":"2017","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.omtm.2020.11.015","article-title":"Low Incidence of Hepatocellular Carcinoma in Mice and Cats Treated with Systemic Adeno-Associated Viral Vectors","volume":"20","author":"Ferla","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/sj.mt.6300325","article-title":"Biochemical, Pathological, and Skeletal Improvement of Mucopolysaccharidosis VI after Gene Transfer to Liver but not to Muscle","volume":"16","author":"Tessitore","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/jgm.302","article-title":"Phenotypic Rescue after Adeno-Associated Virus-Mediated Delivery of 4-Sulfatase to the Retinal Pigment Epithelium of Feline Mucopolysaccharidosis VI","volume":"4","author":"Ho","year":"2002","journal-title":"J. Gene Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/mt.2010.257","article-title":"Long-Term Amelioration of feline Mucopolysaccharidosis VI after AAV-Mediated Liver Gene Transfer","volume":"19","author":"Cotugno","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1089\/hum.2012.179","article-title":"Gene Therapy for Mucopolysaccharidosis Type VI is Effective in Cats Without Pre-Existing Immunity to AAV8","volume":"24","author":"Ferla","year":"2013","journal-title":"Hum. Gene Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.omtm.2020.05.015","article-title":"Liver-Targeted AAV8 Gene Therapy Ameliorates Skeletal and Cardiovascular Pathology in a Mucopolysaccharidosis IVA Murine Model","volume":"18","author":"Sawamoto","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5343","DOI":"10.1038\/s41467-021-25697-y","article-title":"Treatment of Skeletal and Non-Skeletal Alterations of Mucopolysaccharidosis Type IVA by AAV-Mediated Gene Therapy","volume":"12","author":"Bertolin","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1093\/hmg\/ddm223","article-title":"Functional Correction of CNS Lesions in an MPS-IIIA Mouse Model by Intracerebral AAV-Mediated Delivery of Sulfamidase and SUMF1 Genes","volume":"16","author":"Fraldi","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.omtm.2019.10.009","article-title":"Enhancing the Therapeutic Potential of Sulfamidase for the Treatment of Mucopolysaccharidosis IIIA","volume":"15","author":"Sorrentino","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/mt.2015.9","article-title":"Broad Functional Correction of Molecular Impairments by Systemic Delivery of scAAVrh74-hSGSH Gene Delivery in MPS IIIA Mice","volume":"23","author":"Duncan","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"16036","DOI":"10.1038\/mtm.2016.36","article-title":"Functional Correction of Neurological and Somatic Disorders at Later Stages of Disease in MPS IIIA Mice by Systemic scAAV9-hSGSH Gene Delivery","volume":"3","author":"Fu","year":"2016","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.ymthe.2018.01.010","article-title":"Overcoming Limitations Inherent in Sulfamidase to Improve Mucopolysaccharidosis IIIA Gene Therapy","volume":"26","author":"Chen","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.omtm.2019.12.001","article-title":"AAVrh10 Vector Corrects Disease Pathology in MPS IIIA Mice and Achieves Widespread Distribution of SGSH in Large Animal Brains","volume":"17","author":"Hocquemiller","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.omtm.2020.10.014","article-title":"Targeting the Root Cause of Mucopolysaccharidosis IIIA with a New scAAV9 Gene Replacement Vector","volume":"19","author":"Bobo","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1089\/hum.2020.253","article-title":"Systemic scAAV9.U1a.hSGSH Delivery Corrects Brain Biochemistry in Mucopolysaccharidosis Type IIIA at Early and Later Stages of Disease","volume":"32","author":"Saville","year":"2021","journal-title":"Hum. Gene Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1089\/hum.2013.238","article-title":"Intracerebral Administration of Adeno-Associated Viral Vector Serotype rh.10 Carrying Human SGSH and SUMF1 cDNAs in Children With Mucopolysaccharidosis Type IIIA Disease: Results of a Phase I\/II Trial","volume":"25","author":"Tardieu","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1038\/mt.2012.82","article-title":"Hematopoietic Stem Cell and Gene Therapy Corrects Primary Neuropathology and Behavior in Mucopolysaccharidosis IIIA Mice","volume":"20","author":"Wilkinson","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1038\/mt.2013.141","article-title":"Myeloid\/Microglial Driven Autologous Hematopoietic Stem Cell Gene Therapy Corrects a Neuronopathic Lysosomal Disease","volume":"21","author":"Sergijenko","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/jgm.2816","article-title":"Correction of Murine Mucopolysaccharidosis Type IIIA Central Nervous System Pathology by Intracerebroventricular Lentiviral-Mediated Gene Delivery","volume":"16","author":"Mcintyre","year":"2014","journal-title":"J. Gene Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.omtm.2019.04.001","article-title":"Pre-clinical Safety and Efficacy of Lentiviral Vector-Mediated Ex Vivo Stem Cell Gene Therapy for the Treatment of Mucopolysaccharidosis IIIA","volume":"13","author":"Ellison","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ymgme.2010.02.006","article-title":"SGSH Gene Transfer in Mucopolysaccharidosis Type IIIA Mice Using Canine Adenovirus Vectors","volume":"100","author":"Lau","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.gene.2011.09.004","article-title":"Helper-Dependent Canine Adenovirus Vector-Mediated Transgene Expression in a Neurodegenerative Lysosomal Storage Disorder","volume":"491","author":"Lau","year":"2012","journal-title":"Gene"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1093\/hmg\/ddl038","article-title":"Correction of Hunter Syndrome in the MPSII Mouse Model by AAV2\/8-Mediated Gene Delivery","volume":"15","author":"Cardone","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.ajhg.2009.07.011","article-title":"IDS Crossing of the Blood-Brain Barrier Corrects CNS Defects in MPSII Mice","volume":"85","author":"Polito","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s10059-010-0083-2","article-title":"Characterization of a Novel Mucopolysaccharidosis Type II Mouse Model and Recombinant AAV2\/8 Vector-Mediated Gene Therapy","volume":"30","author":"Jung","year":"2010","journal-title":"Mol. Cells"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1089\/hum.2016.101","article-title":"Delivery of an Adeno-Associated Virus Vector into Cerebrospinal Fluid Attenuates Central Nervous System Disease in Mucopolysaccharidosis Type II Mice","volume":"27","author":"Hinderer","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e86696","DOI":"10.1172\/jci.insight.86696","article-title":"CNS-Directed Gene Therapy for the Treatment of Neurologic and Somatic Mucopolysaccharidosis Type II (Hunter Syndrome)","volume":"1","author":"Motas","year":"2016","journal-title":"JCI Insight"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1089\/hum.2016.184","article-title":"Prevention of Neurocognitive Deficiency in Mucopolysaccharidosis Type II Mice by Central Nervous System-Directed, AAV9-Mediated Iduronate Sulfatase Gene Transfer","volume":"28","author":"Laoharawee","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.omtm.2018.07.005","article-title":"Targeting Root Cause by Systemic scAAV9-hIDS Gene Delivery: Functional Correction and Reversal of Severe MPS II in Mice","volume":"10","author":"Fu","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.ymthe.2018.03.002","article-title":"Dose-Dependent Prevention of Metabolic and Neurologic Disease in Murine MPS II by ZFN-Mediated In Vivo Genome Editing","volume":"26","author":"Laoharawee","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.omtm.2018.06.004","article-title":"Toxicology Study of Intra-Cisterna Magna Adeno-Associated Virus 9 Expressing Iduronate-2-Sulfatase in Rhesus Macaques","volume":"10","author":"Hordeaux","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1089\/hum.2014.158","article-title":"Hematopoietic Stem Cell Gene Therapy Corrects Neuropathic Phenotype in Murine Model of Mucopolysaccharidosis Type II","volume":"26","author":"Wakabayashi","year":"2015","journal-title":"Hum. Gene Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e8730","DOI":"10.15252\/emmm.201708730","article-title":"Brain-targeted Stem Cell Gene Therapy Corrects Mucopolysaccharidosis Type II Via Multiple Mechanisms","volume":"10","author":"Gleitz","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.omtm.2020.09.012","article-title":"Ex Vivo Gene Therapy Treats Bone Complications of Mucopolysaccharidosis Type II Mouse Models through Bone Remodeling Reactivation","volume":"19","author":"Wada","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.ymgme.2020.06.007","article-title":"Efficient Engraftment of Genetically Modified Cells Is Necessary to Ameliorate Central Nervous System Involvement of Murine Model of Mucopolysaccharidosis Type II by Hematopoietic Stem Cell Targeted Gene Therapy","volume":"130","author":"Miwa","year":"2020","journal-title":"Mol. Genet. Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.ymthe.2019.03.003","article-title":"Non-viral Delivery of Zinc Finger Nuclease mRNA Enables Highly Efficient In Vivo Genome Editing of Multiple Therapeutic Gene Targets","volume":"27","author":"Conway","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1590\/1678-4685-gmb-2020-0138","article-title":"Updated Birth Prevalence and Relative Frequency of Mucopolysaccharidoses across Brazilian Regions","volume":"44","author":"Josahkian","year":"2021","journal-title":"Genet. Mol. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev.genom.6.080604.162334","article-title":"Sulfatases and Human Disease","volume":"6","author":"Ballabio","year":"2005","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s004399900075","article-title":"The Frequency of Lysosomal Storage Diseases in The Netherlands","volume":"105","author":"Poorthuis","year":"1999","journal-title":"Hum. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ymgme.2016.05.003","article-title":"Molecular Diagnosis of 65 Families with Mucopolysaccharidosis Type II (Hunter Syndrome) Characterized by 16 Novel Mutations in the IDS Gene: Genetic, Pathological, and Structural Studies on Iduronate-2-Sulfatase","volume":"118","author":"Kosuga","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1182\/blood-2014-12-615492","article-title":"In Vivo Genome Editing of the Albumin Locus as a Platform for Protein Replacement Therapy","volume":"126","author":"Sharma","year":"2015","journal-title":"Blood"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1021\/acs.molpharmaceut.2c00365","article-title":"Exciting Times for Lipid Nanoparticles: How Canadian Discoveries Are Enabling Gene Therapies","volume":"19","author":"Cheng","year":"2022","journal-title":"Mol. Pharm."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1126\/science.abm0594","article-title":"CAR T Cells Produced In Vivo to Treat Cardiac Injury","volume":"375","author":"Rurik","year":"2022","journal-title":"Science"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.neuron.2019.02.017","article-title":"Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality","volume":"101","author":"Hudry","year":"2019","journal-title":"Neuron"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"618360","DOI":"10.3389\/fnmol.2021.618360","article-title":"Comparative Effectiveness of Intracerebroventricular, Intrathecal, and Intranasal Routes of AAV9 Vector Administration for Genetic Therapy of Neurologic Disease in Murine Mucopolysaccharidosis Type I","volume":"14","author":"Belur","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1038\/s41467-021-24443-8","article-title":"In Utero Adenine Base Editing Corrects Multi-Organ Pathology in a Lethal Lysosomal Storage Disease","volume":"12","author":"Bose","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"eaba1028","DOI":"10.1126\/sciadv.aba1028","article-title":"Ionizable Lipid Nanoparticles for In Utero mRNA Delivery","volume":"7","author":"Riley","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4690","DOI":"10.1039\/C6CS00076B","article-title":"Blood-Brain Barrier Shuttle Peptides: An Emerging Paradigm for Brain Delivery","volume":"45","author":"Giralt","year":"2016","journal-title":"Chem. Soc. Rev."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"121340","DOI":"10.1016\/j.biomaterials.2021.121340","article-title":"Customized Blood-Brain Barrier Shuttle Peptide to Increase AAV9 Vector Crossing the BBB and Augment Transduction in the Brain","volume":"281","author":"Zhang","year":"2022","journal-title":"Biomaterials"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1089\/crispr.2021.0075","article-title":"A Mutation-Agnostic Hematopoietic Stem Cell Gene Therapy for Metachromatic Leukodystrophy","volume":"5","author":"Antony","year":"2022","journal-title":"Cris. J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1038\/s41467-019-09614-y","article-title":"Gene Correction for SCID-X1 in Long-Term Hematopoietic Stem Cells","volume":"10","author":"Wiebking","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4034","DOI":"10.1038\/s41467-020-17626-2","article-title":"Targeted Gene Correction of Human Hematopoietic Stem Cells for the Treatment of Wiskott-Aldrich Syndrome","volume":"11","author":"Rai","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1016\/j.ymthe.2020.08.004","article-title":"CRISPR-Cas9-Mediated ELANE Mutation Correction in Hematopoietic Stem and Progenitor Cells to Treat Severe Congenital Neutropenia","volume":"28","author":"Tran","year":"2020","journal-title":"Mol. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8153\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:55:46Z","timestamp":1760140546000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,24]]},"references-count":106,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23158153"],"URL":"https:\/\/doi.org\/10.3390\/ijms23158153","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,24]]}}}