Safety and Biodistribution of an Equine Infectious Anemia Virus-Based Gene Therapy, RetinoStat^®, for Age-Related Macular Degeneration

Lentiviral Vector Gene Transfer of Endostatin/Angiostatin for Macular Degeneration (GEM) Study

“…These data are consistent with expression studies in rabbits. 32 The reproducibility of significant transgene levels among patients in each cohort at each time point suggests that subretinal vector injections are quite reliable. Two different approaches for subretinal injection were employed.…”

“…32 The vector was purified and concentrated by anion exchange chromatography and hollow-fiber ultrafiltration. A schematic of the RetinoStat genome is shown in Supplementary Fig.…”

“…Subretinal injections were done as previously described 32 using an early version of RetinoStat in which the RPE-specific vitelliform macular dystrophy 2 promoter was used to express human forms of endostatin and angiostatin. Injections were done in one eye, and the other eye was left untreated.…”

Ocular Gene Delivery Systems Using Ternary Complexes of Plasmid DNA, Polyethylenimine, and Anionic Polymers

“…[1][2][3] The eyes are suitable for topical gene therapy because of their accessibility, ease of monitoring, and their enclosed structure. 2,4,5) Viral vectors such as adenoviral, lentiviral, and adeno-associated virals are commonly used for ocular gene transfer [6][7][8][9] ; however, these viral vectors have some crucial problems such as toxicity, immunogenicity, possible genomic integration, limited size of inserted DNA, and difficult preparative procedures.…”

Gene Therapies for Neovascular Age-Related Macular Degeneration

“…Biodistribution analysis following subretinal administration of this dual vector (RetinoStat, Oxford BioMedica) into rhesus macaques and Dutch belted rabbits showed that the vector was localized within the ocular compartment, tolerated well, and capable of persistent expression (Binley et al 2012). Following subretinal injection, endostatin and angiostatin protein levels peaked in the vitreous of rabbits at 1 mo, and the expression levels persisted for the 6-mo duration of the study.…”