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As corneal transplants are met with high rejection rates in MPS1 children, there remains no treatment to prevent blindness or restore vision in MPS1 children. Since MPS1 is caused by mutations in <jats:italic>idua<\/jats:italic>, which encodes alpha-L-iduronidase, a gene addition strategy to prevent and potentially reverse, MPS1-associated corneal blindness was investigated. Initially, a codon optimized <jats:italic>idua<\/jats:italic> cDNA expression cassette (opt-IDUA) was validated for IDUA production and function following adeno-associated virus (AAV) vector transduction of MPS1 patient fibroblasts. Then, an AAV serotype evaluation in human cornea explants identified an AAV8 and 9 chimeric capsid (8G9) as most efficient for transduction. AAV8G9-opt-IDUA administered to human corneas via intrastromal injection demonstrated widespread transduction, which included cells that naturally produce IDUA and resulted in a &gt;10-fold supraphysiological increase in IDUA activity. No significant apoptosis related to AAV vectors or IDUA was observed under any conditions in both human corneas and MPS1 patient fibroblasts. The collective preclinical data demonstrate safe and efficient IDUA delivery to human corneas, which may prevent and potentially reverse MPS1-associated cornea blindness.<\/jats:p>","DOI":"10.1038\/srep22131","type":"journal-article","created":{"date-parts":[[2016,2,22]],"date-time":"2016-02-22T12:00:11Z","timestamp":1456142411000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["AAV Gene Therapy for MPS1-associated Corneal Blindness"],"prefix":"10.1038","volume":"6","author":[{"given":"Melisa","family":"Vance","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Telmo","family":"Llanga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Will","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenton","family":"Woodard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giridhar","family":"Murlidharan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Chungfat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravind","family":"Asokan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Gilger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Kurtzberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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Jude Samulski is the founder and a shareholder at Asklepios BioPharmaceutical. He receives research support through the University of North Carolina from Asklepios. BioPharmaceutical. He holds patents that have been licensed by UNC to Asklepios. Biopharmaceutical, for which he receives royalties. He has consulted for Baxter Healthcare and has received payment for speaking. Matthew Hirsch has disclosed AAV8G9-optIDUA to the University of North Carolina.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22131"}}