title: Efficient gene delivery to photoreceptors using AAV2/rh10 and rescue of the Rho(-/-) mouse.
abstract: As gene therapies for various forms of retinal degeneration progress toward human clinical trial, it will be essential to have a repertoire of safe and efficient vectors for gene delivery to the target cells. Recombinant adeno-associated virus (AAV) serotype 2/2 has been shown to be well tolerated in the human retina and has provided efficacy in human patients for some inherited retinal degenerations. In this study, the AAV2/8 and AAV2/rh10 serotypes have been compared as a means of gene delivery to mammalian photoreceptor cells using a photoreceptor specific promoter for transgene expression. Both AAV2/8 and AAV2/rh10 provided rescue of the retinal degeneration present in the rhodopsin knockout mouse, with similar levels of benefit as evaluated by molecular, histological, and functional readouts. Transgene expression levels were significantly higher (fivefold) 1 week postsubretinal injection when employing AAV2/8 for rhodopsin gene delivery compared to AAV2/rh10, and were indistinguishable by 6 weeks postadministration of vector. This study reports the use of the AAV2/rh10 serotype to provide rescue in a degenerating retina and provides a comparative evaluation of AAV2/rh10 with respect to AAV2/8, a serotype regarded as providing efficient delivery to photoreceptors.
authors.affiliation: Department of Genetics, School of Genetics and Microbiology, Trinity College Dublin , Dublin 2, Ireland.
authors.forename: Arpad
authors.initials: A
authors.lastname: Palfi
authors.affiliation: Department of Genetics, School of Genetics and Microbiology, Trinity College Dublin , Dublin 2, Ireland.
authors.forename: Naomi
authors.initials: N
authors.lastname: Chadderton
authors.affiliation: Department of Genetics, School of Genetics and Microbiology, Trinity College Dublin , Dublin 2, Ireland.
authors.forename: Mary
authors.initials: M
authors.lastname: O'Reilly
authors.affiliation: Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg-Universität Mainz , Mainz, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Nagel-Wolfrum
authors.affiliation: Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg-Universität Mainz , Mainz, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Wolfrum
authors.affiliation: Center for Advanced Retinal and Ocular Therapeutics, Perelman School Of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Bennett
authors.affiliation: Department of Genetics, School of Genetics and Microbiology, Trinity College Dublin , Dublin 2, Ireland.
authors.forename: Peter
authors.initials: P
authors.lastname: Humphries
authors.affiliation: Department of Genetics, School of Genetics and Microbiology, Trinity College Dublin , Dublin 2, Ireland.
authors.forename: Paul
authors.initials: P
authors.lastname: Kenna
authors.affiliation: Department of Genetics, School of Genetics and Microbiology, Trinity College Dublin , Dublin 2, Ireland.
authors.forename: Sophia
authors.initials: S
authors.lastname: Millington-Ward
authors.affiliation: Department of Genetics, School of Genetics and Microbiology, Trinity College Dublin , Dublin 2, Ireland.
authors.forename: Jane
authors.initials: J
authors.lastname: Farrar