title: Recombinant vectors based on porcine adeno-associated viral serotypes transduce the murine and pig retina.
abstract: Recombinant adeno-associated viral (AAV) vectors are known to safely and efficiently transduce the retina. Among the various AAV serotypes available, AAV2/5 and 2/8 are the most effective for gene transfer to photoreceptors (PR), which are the most relevant targets for gene therapy of inherited retinal degenerations. However, the search for novel AAV serotypes with improved PR transduction is ongoing. In this work we tested vectors derived from five AAV serotypes isolated from porcine tissues (referred to as porcine AAVs, four of which are newly identified) for their ability to transduce both the murine and the cone-enriched pig retina. Porcine AAV vectors expressing EGFP under the control of the CMV promoter were injected subretinally either in C57BL/6 mice or Large White pigs. The resulting retinal tropism was analyzed one month later on histological sections, while levels of PR transduction were assessed by Western blot. Our results show that all porcine AAV transduce murine and porcine retinal pigment epithelium and PR upon subretinal administration. AAV2/po1 and 2/po5 are the most efficient porcine AAVs for murine PR transduction and exhibit the strongest tropism for pig cone PR. The levels of PR transduction obtained with AAV2/po1 and 2/po5 are similar, albeit not superior, to those obtained with AAV2/5 and AAV2/8, which evinces AAV2/po1 and 2/po5 to be promising vectors for retinal gene therapy.
authors.affiliation: Telethon Institute of Genetics and Medicine, Napoli, Italy.
authors.forename: Agostina
authors.initials: A
authors.lastname: Puppo
authors.forename: Alexander
authors.initials: A
authors.lastname: Bello
authors.forename: Anna
authors.initials: A
authors.lastname: Manfredi
authors.forename: Giulia
authors.initials: G
authors.lastname: Cesi
authors.forename: Elena
authors.initials: E
authors.lastname: Marrocco
authors.forename: Michele
authors.initials: M
authors.lastname: Della Corte
authors.forename: Settimio
authors.initials: S
authors.lastname: Rossi
authors.forename: Massimo
authors.initials: M
authors.lastname: Giunti
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Bacci
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonelli
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Surace
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
authors.forename: Alberto
authors.initials: A
authors.lastname: Auricchio
mesh_terms: D000818:Animals; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D051379:Mice; D012160:Retina; D013552:Swine; D014161:Transduction, Genetic / Q000379:methods*