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However, AAV's limited cargo capacity prevents its application to therapies of inherited retinal diseases due to mutations of genes over 5\u00a0kb, like Stargardt's disease (STGD) and Usher syndrome type IB (USH1B). Previous methods based on \u2018forced\u2019 packaging of large genes into AAV capsids may not be easily translated to the clinic due to the generation of genomes of heterogeneous size which raise safety concerns. Taking advantage of AAV's ability to concatemerize, we generated dual AAV vectors which reconstitute a large gene by either splicing (trans\u2010splicing), homologous recombination (overlapping), or a combination of the two (hybrid). We found that dual trans\u2010splicing and hybrid vectors transduce efficiently mouse and pig photoreceptors to levels that, albeit lower than those achieved with a single AAV, resulted in significant improvement of the retinal phenotype of mouse models of STGD and USH1B. Thus, dual AAV trans\u2010splicing or hybrid vectors are an attractive strategy for gene therapy of retinal diseases that require delivery of large genes.<\/jats:p>","DOI":"10.1002\/emmm.201302948","type":"journal-article","created":{"date-parts":[[2013,10,22]],"date-time":"2013-10-22T00:50:58Z","timestamp":1382403058000},"page":"194-211","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":264,"title":["Effective delivery of large genes to the retina by dual AAV vectors"],"prefix":"10.1038","volume":"6","author":[{"given":"Ivana","family":"Trapani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasqualina","family":"Colella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Sommella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Iodice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Cesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"de Simone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Marrocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Settimio","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Giunti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpad","family":"Palfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwyneth J","family":"Farrar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Polishchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Auricchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,12,16]]},"reference":[{"key":"BFEMMM201302948_CR1","first-page":"122","volume":"17","author":"R Allikmets","year":"1997","unstructured":"Allikmets R (1997) A photoreceptor cell\u2010specific ATP\u2010binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. 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