Safety and biodistribution of an equine infectious anemia virus-based gene therapy, RetinoStat(®), for age-related macular degeneration
| Autor: | James Miskin, Georgina Ferrige, Michelle Kelleher, Katie Binley, Vladimir Bantseev, Paul E. Miller, T Michael Nork, Diana Angell-Manning, Stuart Naylor, Peter Widdowson, Kyriacos A. Mitrophanous, Jackie de Belin, Julie Loader, Marie Carlucci, Margaret Esapa, Scott Ellis, Daniel Chipchase |
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| Rok vydání: | 2012 |
| Předmět: |
Pathology
medicine.medical_specialty Intraocular pressure Biodistribution Time Factors genetic structures Genetic enhancement Genetic Vectors Virus Equine infectious anemia Macular Degeneration Genetics medicine Animals Humans Molecular Biology Angiostatins Angiostatin biology business.industry Genetic Therapy Macular degeneration biology.organism_classification medicine.disease Macaca mulatta eye diseases Endostatins Vitreous Body Leukocytes Mononuclear Molecular Medicine sense organs Rabbits Endostatin business Infectious Anemia Virus Equine |
| Zdroj: | Human gene therapy. 23(9) |
| ISSN: | 1557-7422 |
| Popis: | RetinoStat(®) is an equine infectious anemia virus-based lentiviral gene therapy vector that expresses the angiostatic proteins endostatin and angiostatin that is delivered via a subretinal injection for the treatment of the wet form of age-related macular degeneration. We initiated 6-month safety and biodistribution studies in two species; rhesus macaques and Dutch belted rabbits. After subretinal administration of RetinoStat the level of human endostatin and angiostatin proteins in the vitreous of treated rabbit eyes peaked at ∼1 month after dosing and remained elevated for the duration of the study. Regular ocular examinations revealed a mild to moderate transient ocular inflammation that resolved within 1 month of dosing in both species. There were no significant long-term changes in the electroretinograms or intraocular pressure measurements in either rabbits or macaques postdosing compared with the baseline reading in RetinoStat-treated eyes. Histological evaluation did not reveal any structural changes in the eye although there was an infiltration of mononuclear cells in the vitreous, retina, and choroid. No antibodies to any of the RetinoStat vector components or the transgenes could be detected in the serum from either species, and biodistribution analysis demonstrated that the RetinoStat vector was maintained within the ocular compartment. In summary, these studies found RetinoStat to be well tolerated, localized, and capable of persistent expression after subretinal delivery. |
| Databáze: | OpenAIRE |
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