{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:13:28Z","timestamp":1787228008701,"version":"build-2736575974"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2018,10]]},"DOI":"10.1038\/s41390-018-0095-8","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T14:20:33Z","timestamp":1539613233000},"page":"545-551","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Tailoring the AAV2 capsid vector for bone-targeting"],"prefix":"10.1038","volume":"84","author":[{"given":"Carlos J.","family":"Alm\u00e9ciga-D\u00edaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana M.","family":"Monta\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis A.","family":"Barrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunji","family":"Tomatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,15]]},"reference":[{"key":"95_CR1","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1053\/j.seminhematol.2009.10.008","volume":"47","author":"VK Prasad","year":"2010","unstructured":"Prasad, V. K. & Kurtzberg, J. Transplant outcomes in mucopolysaccharidoses. Semin. Hematol. 47, 59\u201369 (2010).","journal-title":"Semin. Hematol."},{"key":"95_CR2","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1146\/annurev-genom-090711-163739","volume":"13","author":"RJ Desnick","year":"2012","unstructured":"Desnick, R. J. & Schuchman, E. H. Enzyme replacement therapy for lysosomal diseases: lessons from 20 years of experience and remaining challenges. Annu. Rev. Genom. Hum. Genet. 13, 307\u2013335 (2012).","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"issue":"Suppl 1","key":"95_CR3","first-page":"99","volume":"11","author":"NS Yew","year":"2013","unstructured":"Yew, N. S. & Cheng, S. H. Gene therapy for lysosomal storage disorders. Pediatr. Endocrinol. Rev. 11(Suppl 1), 99\u2013109 (2013).","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"95_CR4","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.ymgme.2013.04.002","volume":"110","author":"CJ Hendriksz","year":"2013","unstructured":"Hendriksz, C. J. et al. Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA. Mol. Genet. Metab. 110, 54\u201364 (2013).","journal-title":"Mol. Genet. Metab."},{"key":"95_CR5","unstructured":"Brooks, M. FDA clears the first drug for rare Morquio A syndrome. Medscape (2014)."},{"key":"95_CR6","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.2147\/DDDT.S68562","volume":"9","author":"S Tomatsu","year":"2015","unstructured":"Tomatsu, S. et al. Impact of enzyme replacement therapy and hematopoietic stem cell transplantation in patients with Morquio A syndrome. Drug Des. Devel Ther. 9, 1937\u20131953 (2015).","journal-title":"Drug Des. Devel Ther."},{"key":"95_CR7","first-page":"741","volume":"5","author":"Y Puckett","year":"2017","unstructured":"Puckett, Y., Mullinder, H. & Monta\u00f1o, A. M. Enzyme replacement therapy with elosulfase alfa for Mucopolysaccharidosis IVA (Morquio A Syndrome): milestones and challenges. expert rev orphan. Drugs 5, 741\u2013752 (2017).","journal-title":"Drugs"},{"key":"95_CR8","volume-title":"Principles of Bone Biology","author":"JP Bilezikian","year":"2008","unstructured":"Bilezikian, J. P., Raisz, L. G. & Martin, J. Principles of Bone Biology (Academic Press, San Diego, CA, 2008)."},{"key":"95_CR9","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3109\/10611869808995866","volume":"5","author":"J Fujisaki","year":"1998","unstructured":"Fujisaki, J. et al. Osteotropic drug delivery system (ODDS) based on bisphosphonic prodrug. I.v. effects of osteotropic estradiol on bone mineral density and uterine weight in ovariectomized rats. J. Drug. Target. 5, 129\u2013138 (1998).","journal-title":"J. Drug. Target."},{"key":"95_CR10","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1016\/j.addr.2004.12.011","volume":"57","author":"D Wang","year":"2005","unstructured":"Wang, D., Miller, S. C., Kopeckov\u00e1, P. & Kopecek, J. Bone-targeting macromolecular therapeutics. Adv. Drug Deliv. Rev. 57, 1049\u20131076 (2005).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"95_CR11","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1359\/jbmr.2000.15.5.936","volume":"15","author":"S Kasugai","year":"2000","unstructured":"Kasugai, S., Fujisawa, R., Waki, Y., Miyamoto, K. & Ohya, K. Selective drug delivery system to bone: small peptide (Asp)6 conjugation. J. Bone Miner. Res. 15, 936\u2013943 (2000).","journal-title":"J. Bone Miner. Res."},{"key":"95_CR12","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1210\/endo.142.3.8024","volume":"142","author":"K Yokogawa","year":"2001","unstructured":"Yokogawa, K. et al. Selective delivery of estradiol to bone by aspartic acid oligopeptide and its effects on ovariectomized mice. Endocrinology 142, 1228\u20131233 (2001).","journal-title":"Endocrinology"},{"key":"95_CR13","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.ymgme.2006.02.012","volume":"88","author":"T Nishioka","year":"2006","unstructured":"Nishioka, T. et al. Enhancement of drug delivery to bone: characterization of human tissue-nonspecific alkaline phosphatase tagged with an acidic oligopeptide. Mol. Genet. Metab. 88, 244\u2013255 (2006).","journal-title":"Mol. Genet. Metab."},{"issue":"6","key":"95_CR14","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1359\/jbmr.071213","volume":"23","author":"Jos\u00e9 Luis Mill\u00e1n","year":"2007","unstructured":"Millan, J. L., et al. Enzyme replacement therapy for murine hypophosphatasia. J. Bone Miner. Res. 23, 777\u2013787 (2018).","journal-title":"Journal of Bone and Mineral Research"},{"key":"95_CR15","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.ymgme.2008.01.007","volume":"94","author":"AM Monta\u00f1o","year":"2008","unstructured":"Monta\u00f1o, A. M. et al. Acidic amino acid tag enhances response to enzyme replacement in mucopolysaccharidosis type VII. Mol. Genet. Metab. 94, 178\u2013189 (2008).","journal-title":"Mol. Genet. Metab."},{"key":"95_CR16","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1038\/mt.2010.32","volume":"18","author":"S Tomatsu","year":"2010","unstructured":"Tomatsu, S. et al. Enhacement of drug delivery: enzyme-replacement therapy for murine Morquio A syndrome. Mol. Ther. 18, 1094\u20131102 (2010).","journal-title":"Mol. Ther."},{"key":"95_CR17","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1089\/hum.2010.210","volume":"22","author":"T Matsumoto","year":"2011","unstructured":"Matsumoto, T. et al. Rescue of severe infantile hypophosphatasia mice by AAV-mediated sustained expression of soluble alkaline phosphatase. Hum. Gene Ther. 22, 1355\u20131364 (2011).","journal-title":"Hum. Gene Ther."},{"key":"95_CR18","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0065-2660(09)67002-4","volume":"67","author":"S Michelfelder","year":"2009","unstructured":"Michelfelder, S. & Trepel, M. Adeno-associated viral vectors and their redirection to cell-type specific receptors. Adv. Genet. 67, 29\u201360 (2009).","journal-title":"Adv. Genet."},{"key":"95_CR19","doi-asserted-by":"publisher","first-page":"8635","DOI":"10.1128\/JVI.74.18.8635-8647.2000","volume":"74","author":"P Wu","year":"2000","unstructured":"Wu, P. et al. Mutational analysis of the adeno-associated virus type 2 (AAV2) capsid gene and construction of AAV2 vectors with altered tropism. J. Virol. 74, 8635\u20138647 (2000).","journal-title":"J. Virol."},{"key":"95_CR20","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1038\/sj.gt.3302046","volume":"10","author":"S Loiler","year":"2003","unstructured":"Loiler, S. et al. Targeting recombinant adeno-associated virus vectors to enhance gene transfer to pancreatic islets and liver. Gene Ther. 10, 1551\u20131558 (2003).","journal-title":"Gene Ther."},{"key":"95_CR21","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s11095-007-9431-0","volume":"25","author":"I Kwon","year":"2008","unstructured":"Kwon, I. & Schaffer, D. V. Designer gene delivery vectors: molecular engineering and evolution of adeno-associated viral vectors for enhanced gene transfer. Pharm. Res. 25, 489\u2013499 (2008).","journal-title":"Pharm. Res."},{"key":"95_CR22","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1038\/gt.2009.59","volume":"16","author":"CY Yu","year":"2009","unstructured":"Yu, C. Y. et al. A muscle-targeting peptide displayed on AAV2 improves muscle tropism on systemic delivery. Gene Ther. 16, 953\u2013962 (2009).","journal-title":"Gene Ther."},{"key":"95_CR23","doi-asserted-by":"publisher","DOI":"10.1186\/1479-0556-10-3","volume":"10","author":"NC Lee","year":"2012","unstructured":"Lee, N. C. et al. An acidic oligopeptide displayed on AAV2 improves axial muscle tropism after systemic delivery. Genet. Vaccin. Ther. 10, 3 (2012).","journal-title":"Genet. Vaccin. Ther."},{"key":"95_CR24","doi-asserted-by":"publisher","first-page":"e5122","DOI":"10.1371\/journal.pone.0005122","volume":"4","author":"S Michelfelder","year":"2009","unstructured":"Michelfelder, S. et al. Successful expansion but not complete restriction of tropism of adeno-associated virus by in vivo biopanning of random virus display peptide libraries. PLoS ONE 4, e5122 (2009).","journal-title":"PLoS ONE"},{"key":"95_CR25","unstructured":"Stewart, T. & Mann, V. in Methodos in Molecular Medicine: Bone Research Protocols (eds Helfrich, M. & Ralston, S.) pp 425\u2013432 (Humana Press Inc., Totowa, NJ, 2003)."},{"key":"95_CR26","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1093\/hmg\/ddm353","volume":"17","author":"S Tomatsu","year":"2008","unstructured":"Tomatsu, S. et al. Enzyme replacement therapy in a murine model of Morquio A syndrome. Hum. Mol. Genet. 17, 815\u2013824 (2008).","journal-title":"Hum. Mol. Genet."},{"key":"95_CR27","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 9, 671\u2013675 (2012).","journal-title":"Nat. Methods"},{"key":"95_CR28","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.biotechadv.2007.09.001","volume":"26","author":"MG Aucoin","year":"2008","unstructured":"Aucoin, M. G., Perrier, M. & Kamen, A. A. Critical assessment of current adeno-associated viral vector production and quantification methods. Biotechnol. Adv. 26, 73\u201388 (2008).","journal-title":"Biotechnol. Adv."},{"key":"95_CR29","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1007\/s11033-008-9392-3","volume":"36","author":"CJ Almeciga-Diaz","year":"2009","unstructured":"Almeciga-Diaz, C. J. et al. Effect of elongation factor 1alpha promoter and SUMF1 over in vitro expression of N-acetylgalactosamine-6-sulfate sulfatase. Mol. Biol. Rep. 36, 1863\u20131870 (2009).","journal-title":"Mol. Biol. Rep."},{"key":"95_CR30","doi-asserted-by":"publisher","first-page":"3608","DOI":"10.1111\/j.1742-4658.2010.07769.x","volume":"277","author":"C Alm\u00e9ciga-D\u00edaz","year":"2010","unstructured":"Alm\u00e9ciga-D\u00edaz, C., Monta\u00f1o, A. M., Tomatsu, S. & Barrera, L. Adeno-associated virus gene transfer on Morquio A: effect of promoters and sulfatase-modifying Factor 1. FEBS J. 277, 3608\u20133619 (2010).","journal-title":"FEBS J."},{"key":"95_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/17453690610046512","volume":"78","author":"M Ulrich-Vinther","year":"2007","unstructured":"Ulrich-Vinther, M. Gene therapy methods in bone and joint disorders. Evaluation of the adeno-associated virus vector in experimental models of articular cartilage disorders, periprosthetic osteolysis and bone healing. Acta Orthop. Suppl. 78, 1\u201364 (2007).","journal-title":"Acta Orthop. Suppl."},{"key":"95_CR32","doi-asserted-by":"publisher","first-page":"7265","DOI":"10.1128\/JVI.00076-06","volume":"80","author":"L Perabo","year":"2006","unstructured":"Perabo, L. et al. Heparan sulfate proteoglycan binding properties of adeno-associated virus retargeting mutants and consequences for their in vivo tropism. J. Virol. 80, 7265\u20137269 (2006).","journal-title":"J. Virol."},{"key":"95_CR33","doi-asserted-by":"publisher","first-page":"10405","DOI":"10.1073\/pnas.162250899","volume":"99","author":"Q Xie","year":"2002","unstructured":"Xie, Q. et al. The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy. Proc. Natl Acad. Sci. USA 99, 10405\u201310410 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"95_CR34","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/mt.2008.76","volume":"16","author":"C Zincarelli","year":"2008","unstructured":"Zincarelli, C., Soltys, S., Rengo, G. & Rabinowitz, J. E. Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol. Ther. 16, 1073\u20131080 (2008).","journal-title":"Mol. Ther."},{"key":"95_CR35","doi-asserted-by":"publisher","first-page":"6995","DOI":"10.1128\/JVI.77.12.6995-7006.2003","volume":"77","author":"SR Opie","year":"2003","unstructured":"Opie, S. R., Warrington, K. H. Jr., Agbandje-McKenna, M., Zolotukhin, S. & Muzyczka, N. Identification of amino acid residues in the capsid proteins of adeno-associated virus type 2 that contribute to heparan sulfate proteoglycan binding. J. Virol. 77, 6995\u20137006 (2003).","journal-title":"J. Virol."},{"key":"95_CR36","doi-asserted-by":"publisher","first-page":"2007","DOI":"10.1089\/104303401753204571","volume":"12","author":"G Toietta","year":"2001","unstructured":"Toietta, G. et al. Various cells retrovirally transduced with N-acetylgalactosamine-6-sulfate sulfatase correct Morquio skin fibroblasts in vitro. Hum. Gene Ther. 12, 2007\u20132016 (2001).","journal-title":"Hum. Gene Ther."},{"key":"95_CR37","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/sj.gt.3302961","volume":"14","author":"H Fu","year":"2007","unstructured":"Fu, H. et al. Significantly increased lifespan and improved behavioral performances by rAAV gene delivery in adult mucopolysaccharidosis IIIB mice. Gene Ther. 14, 1065\u20131077 (2007).","journal-title":"Gene Ther."},{"key":"95_CR38","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1093\/hmg\/ddl038","volume":"15","author":"M Cardone","year":"2006","unstructured":"Cardone, M. et al. Correction of Hunter syndrome in the MPSII mouse model by AAV2\/8-mediated gene delivery. Hum. Mol. Genet. 15, 1225\u20131236 (2006).","journal-title":"Hum. Mol. Genet."},{"key":"95_CR39","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1016\/j.ymthe.2004.03.011","volume":"9","author":"SD Hartung","year":"2004","unstructured":"Hartung, S. D. et al. Correction of metabolic, craniofacial, and neurologic abnormalities in MPS I mice treated at birth with adeno-associated virus vector transducing the human A-L-iduronidase gene. Mol. Ther. 9, 866\u2013875 (2004).","journal-title":"Mol. Ther."}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41390-018-0095-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41390-018-0095-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41390-018-0095-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:23:32Z","timestamp":1684617812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-018-0095-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["95"],"URL":"https:\/\/doi.org\/10.1038\/s41390-018-0095-8","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10]]},"assertion":[{"value":"16 January 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2018","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors have US patent 7,972,593 issued on 5 July 2011. The patent covers the underlying concept of AAV vector with bone targeting described in the manuscript. S.T. was a former employee at Saint Louis University, where the experiments were conducted and completed.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}