{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:11:31Z","timestamp":1789618291842,"version":"build-2803163510"},"reference-count":27,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,4,15]]},"abstract":"<jats:p>Sulfatases are enzymes that hydrolyse a diverse range of sulfate esters. Deficiency of lysosomal sulfatases leads to human diseases characterized by the accumulation of either GAGs (glycosaminoglycans) or sulfolipids. The catalytic activity of sulfatases resides in a unique formylglycine residue in their active site generated by the post-translational modification of a highly conserved cysteine residue. This modification is performed by SUMF1 (sulfatase-modifying factor 1), which is an essential factor for sulfatase activities. Mutations in the SUMF1 gene cause MSD (multiple sulfatase deficiency), an autosomal recessive disease in which the activities of all sulfatases are profoundly reduced. In previous studies, we have shown that SUMF1 has an enhancing effect on sulfatase activity when co-expressed with sulfatase genes in COS-7 cells. In the present study, we demonstrate that SUMF1 displays an enhancing effect on sulfatases activity when co-delivered with a sulfatase cDNA via AAV (adeno-associated virus) and LV (lentivirus) vectors in cells from individuals affected by five different diseases owing to sulfatase deficiencies or from murine models of the same diseases [i.e. MLD (metachromatic leukodystrophy), CDPX (X-linked dominant chondrodysplasia punctata) and MPS (mucopolysaccharidosis) II, IIIA and VI]. The SUMF1-enhancing effect on sulfatase activity resulted in an improved clearance of the intracellular GAG or sulfolipid accumulation. Moreover, we demonstrate that the SUMF1-enhancing effect is also present in vivo after AAV-mediated delivery of the sulfamidase gene to the muscle of MPSIIIA mice, resulting in a more efficient rescue of the phenotype. These results indicate that co-delivery of SUMF1 may enhance the efficacy of gene therapy in several sulfatase deficiencies.<\/jats:p>","DOI":"10.1042\/bj20061783","type":"journal-article","created":{"date-parts":[[2007,3,26]],"date-time":"2007-03-26T15:15:17Z","timestamp":1174922117000},"page":"305-312","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["SUMF1 enhances sulfatase activities<i>in vivo<\/i>in five sulfatase deficiencies"],"prefix":"10.1042","volume":"403","author":[{"given":"Alessandro","family":"Fraldi","sequence":"first","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino, 111, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Biffi","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), H. San Raffaele Scientific Institute, Milan 20132, Italy"},{"name":"Vita Salute San Raffaele University Medical School, H. San Raffaele Scientific Institute, Milan 20132, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino, 111, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Visigalli","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), H. San Raffaele Scientific Institute, Milan 20132, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Pepe","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino, 111, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Settembre","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino, 111, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Nusco","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino, 111, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Auricchio","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino, 111, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Naldini","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), H. San Raffaele Scientific Institute, Milan 20132, Italy"},{"name":"Vita Salute San Raffaele University Medical School, H. San Raffaele Scientific Institute, Milan 20132, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ballabio","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino, 111, 80131 Naples, Italy"},{"name":"Medical Genetics, Department of Pediatrics, Faculty of Medicine, Federico II University, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria\u00a0Pia","family":"Cosma","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino, 111, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2007,3,26]]},"reference":[{"key":"2021112213081284000_B1","first-page":"3725","article-title":"Multiple sulfatase deficiency and the nature of the sulfatase family","volume-title":"The Metabolic and Molecular Basis of Inherited Disease","author":"Hopwood","year":"2001"},{"key":"2021112213081284000_B2","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev.genom.6.080604.162334","article-title":"Sulfatases and human disease","volume":"6","author":"Diez-Roux","year":"2005","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"2021112213081284000_B3","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1093\/hmg\/ddi351","article-title":"Sulfatases and sulfatase modifying factors: an exclusive and promiscuous relationship","volume":"14","author":"Sardiello","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"2021112213081284000_B4","first-page":"3695","article-title":"Metachromatic leukodystrophy","volume-title":"The Metabolic and Molecular Basis of Inherited Disease","author":"Von\u00a0Figura","year":"2001"},{"key":"2021112213081284000_B5","first-page":"3421","article-title":"The mucopolysaccharidoses","volume-title":"The Metabolic and Molecular Basis of Inherited Disease","author":"Neufeld","year":"2001"},{"key":"2021112213081284000_B6","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/0092-8674(87)90447-8","article-title":"Cloning and expression of steroid sulfatase cDNA and the frequent occurrence of deletions in STS deficiency: implications for X\u2013Y interchange","volume":"49","author":"Yen","year":"1987","journal-title":"Cell"},{"key":"2021112213081284000_B7","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0092-8674(95)90367-4","article-title":"A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata (CDPX) and implications for warfarin embryopathy","volume":"81","author":"Franco","year":"1995","journal-title":"Cell"},{"key":"2021112213081284000_B8","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0092-8674(95)90314-3","article-title":"A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency","volume":"82","author":"Schmidt","year":"1995","journal-title":"Cell"},{"key":"2021112213081284000_B9","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S0092-8674(03)00348-9","article-title":"The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases","volume":"113","author":"Cosma","year":"2003","journal-title":"Cell"},{"key":"2021112213081284000_B10","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\u03b1-formylglycine generating enzyme","volume":"113","author":"Dierks","year":"2003","journal-title":"Cell"},{"key":"2021112213081284000_B11","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1089\/hum.2005.16.929","article-title":"Coexpression of formylglycine-generating enzyme is essential for synthesis and secretion of functional arylsulfatase A in a mouse model of metachromatic leukodystrophy","volume":"16","author":"Takakusaki","year":"2005","journal-title":"Hum. Gene Ther."},{"key":"2021112213081284000_B12","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1172\/JCI200419205","article-title":"Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells","volume":"113","author":"Biffi","year":"2004","journal-title":"J. Clin. Invest."},{"key":"2021112213081284000_B13","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1089\/104303401450988","article-title":"Isolation of highly infectious and pure adeno-associated virus type\u00a02 vectors with a single-step gravity-flow column","volume":"12","author":"Auricchio","year":"2001","journal-title":"Hum. Gene Ther."},{"key":"2021112213081284000_B14","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":"2021112213081284000_B15","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1093\/hmg\/10.26.3075","article-title":"Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a model","volume":"10","author":"Auricchio","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"2021112213081284000_B16","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780199636778.001.0001","article-title":"Laboratory Protocols for Conditional Gene Targeting","author":"Torres","year":"1997"},{"key":"2021112213081284000_B17","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1002\/humu.20040","article-title":"Molecular and functional analysis of SUMF1 mutations in multiple sulfatase deficiency","volume":"23","author":"Cosma","year":"2004","journal-title":"Hum. Mutat."},{"key":"2021112213081284000_B18","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1007\/BF01799255","article-title":"A fluorimetric enzyme assay for the diagnosis of Sanfilippo disease type\u00a0A (MPS IIIA)","volume":"19","author":"Karpova","year":"1996","journal-title":"J. Inherit. Metab. Dis."},{"key":"2021112213081284000_B19","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1023\/A:1012763026526","article-title":"A fluorimetric enzyme assay for the diagnosis of MPS II (Hunter disease)","volume":"24","author":"Voznyi","year":"2001","journal-title":"J. Inherit. Metab. Dis."},{"key":"2021112213081284000_B20","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1093\/glycob\/9.12.1389","article-title":"A mouse model for mucopolysaccharidosis type\u00a0IIIA (Sanfilippo syndrome)","volume":"9","author":"Bhaumik","year":"1999","journal-title":"Glycobiology"},{"key":"2021112213081284000_B21","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":"2021112213081284000_B22","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. Invest."},{"key":"2021112213081284000_B23","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nbt1049","article-title":"Coordinate dual-gene transgenesis by lentiviral vectors carrying synthetic bidirectional promoters","volume":"23","author":"Amendola","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"2021112213081284000_B24","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1093\/glycob\/11.1.99","article-title":"A novel missense mutation in lysosomal sulfamidase is the basis of MPS III A in a spontaneous mouse mutant","volume":"11","author":"Bhattacharyya","year":"2001","journal-title":"Glycobiology"},{"key":"2021112213081284000_B25","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1203\/01.PDR.0000129661.40499.12","article-title":"Enzyme-replacement therapy from birth delays the development of behavior and learning problems in mucopolysaccharidosis type\u00a0IIIA mice","volume":"56","author":"Gliddon","year":"2004","journal-title":"Pediatr. Res."},{"key":"2021112213081284000_B26","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.bbr.2004.08.019","article-title":"Development of motor deficits in a murine model of mucopolysaccharidosis type\u00a0IIIA (MPS-IIIA)","volume":"158","author":"Hemsley","year":"2005","journal-title":"Behav. Brain Res."},{"key":"2021112213081284000_B27","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."}],"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/403\/2\/305\/646716\/bj4030305.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/403\/2\/305\/646716\/bj4030305.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T10:40:27Z","timestamp":1707734427000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/403\/2\/305\/41656\/SUMF1-enhances-sulfatase-activities-in-vivo-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3,26]]},"references-count":27,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2007,4,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20061783","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3,26]]}}}