AAV-mediated photoreceptor transduction of the pig cone-enriched retina

• DOI: 10.1038/gt.2011.3
• Publication Date: 2011-03-17T11:31:05Z
• Authors: C Mussolino; M della Corte; S Rossi; F Viola; U Di Vicino; E Marrocco; S Neglia; M Doria; F Testa; R Giovannoni; M Crasta; M Giunti; E Villani; M Lavitrano; M L Bacci; R Ratiglia; F Simonelli; A Auricchio; E M Surace
• Keywords: Transduction (biophysics); Adeno-associated virus; Photoreceptor cell; Visual phototransduction; Muller glia

Recent success in clinical trials supports the use of adeno-associated viral (AAV) vectors for gene therapy retinal diseases caused by defects pigment epithelium (RPE). In contrast, evidence efficacy AAV-mediated transfer to photoreceptors, major site inherited diseases, is less robust. addition, although RPE transduction appears efficient, independently serotype used and species treated, photoreceptor has not been systematically investigated thus so far large animal models, which also may allow identifying relevant species-specific differences transduction. present study, we porcine retina, a high cone/rod ratio. This feature allows properly evaluate both cone rod photoreceptors compare characteristics AAV2/5 2/8, two most efficient AAV vector serotypes targeting. Here show that 2/8 transduces photoreceptors. AAV2/8 infects more efficiently than AAV2/5, similarly what have observed murine retina. The photoreceptor-specific rhodopsin promoter restricts transgene expression rods cones, results levels similar those obtained with ubiquitous promoters tested. Finally, immunological, toxicological biodistribution studies support safety subretinal administration data presented here on cone-enriched retina affect development gene-based therapies rare common severe diseases.