title: Retinal transduction profiles by high-capacity viral vectors.
abstract: Retinal gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. However, the limited cargo capacity of AAV prevents their use for therapy of those inherited retinopathies (IRs) due to mutations in large (>5 kb) genes. Viral vectors derived from adenovirus (Ad), lentivirus (LV) and herpes virus (HV) can package large DNA sequences, but do not target efficiently retinal photoreceptors (PRs) where the majority of genes responsible for IRs are expressed. Here, we have evaluated the mouse retinal transduction profiles of vectors derived from 16 different Ad serotypes, 7 LV pseudotypes and from a bovine HV. Most of the vectors tested transduced efficiently the retinal pigment epithelium. We found that LV-GP64 tends to transduce more PRs than the canonical LV-VSVG, albeit this was restricted to a narrow region. We observed more extensive PR transduction with HdAd1, 2 and 5/F35++ than with LV, although none of them outperformed the canonical HdAd5 or matched the extension of PR transduction achieved with AAV2/8.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Puppo
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cesi
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Marrocco
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Piccolo
authors.affiliation: Department of Medical Veterinary Science, University of Parma, Parma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Jacca
authors.affiliation: Lowance Center for Human Immunology, Departments of Pediatrics and Medicine, Emory University, Atlanta, GA, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Shayakhmetov
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: R J
authors.initials: RJ
authors.lastname: Parks
authors.affiliation: Departments of Internal Medicine, Neurology and Molecular Physiology & Biophysics, University of Iowa, Iowa City, IA, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Davidson
authors.affiliation: Okairos, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Colloca
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Brunetti-Pierri
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: P
authors.initials: P
authors.lastname: Ng
authors.affiliation: Department of Medical Veterinary Science, University of Parma, Parma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Donofrio
authors.affiliation: 1] Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy [2] Medical Genetics, Department of Translational Medicine, University of Naples Federico II, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Auricchio
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000145:classification / Q000235:genetics*; D004596:Electroretinography; D004847:Epithelial Cells / Q000821:virology; D005822:Genetic Vectors / Q000008:administration & dosage; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D026021:Herpesvirus 4, Bovine / Q000145:classification / Q000235:genetics*; D016086:Lentivirus / Q000145:classification / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000821:virology*; D014161:Transduction, Genetic
chemical_list: D049452:Green Fluorescent Proteins