Transduction of Photoreceptors With Equine Infectious Anemia Virus Lentiviral Vectors: Safety and Biodistribution of StarGen for Stargardt Disease
Open accessAbstract
PURPOSE: StarGen is an equine infectious anemia virus (EIAV)-based lentiviral vector that expresses the photoreceptor-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) protein that is mutated in Stargardt disease (STGD1), a juvenile macular dystrophy. EIAV vectors are able to efficiently transduce rod and cone photoreceptors in addition to retinal pigment epithelium in the adult macaque and rabbit retina following subretinal delivery. The safety and biodistribution of StarGen following subretinal delivery in macaques and rabbits was assessed. METHODS: Regular ophthalmic examinations, IOP measurements, ERG responses, and histopathology were carried out in both species to compare control and vector-treated eyes. Tissue and fluid samples were obtained to evaluate the persistence, biodistribution, and shedding of the vector following subretinal delivery. RESULTS: Ophthalmic examinations revealed a slightly higher level of inflammation in StarGen compared with control treated eyes in both species. However, inflammation was transient and no overt toxicity was observed in StarGen treated eyes and there were no abnormal clinical findings. There was no StarGen-associated rise in IOP or abnormal ERG response in either rabbits or macaques. Histopathologic examination of the eyes did not reveal any detrimental changes resulting from subretinal administration of StarGen. Although antibodies to StarGen vector components were detected in rabbit but not macaque serum, this immunologic response did not result in any long-term toxicity. Biodistribution analysis demonstrated that the StarGen vector was restricted to the ocular compartment. CONCLUSIONS: In summary, these studies demonstrate StarGen to be well tolerated and localized following subretinal administration.
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In general, multiple studies have shown that lentiviruses are relatively safe and can result in effective and sustained gene transduction for a significant time.
“In general, multiple studies have shown that lentiviruses are relatively safe and can result in effective and sustained gene transduction for a significant time.”
From Ocular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses (2022) · cites this paper as [28]
The Discussion (page unavailable) says subretinal lentiviral delivery consistently produces efficient, stable transduction of retinal pigment epithelial cells, and reports efficient transduction with the EIAV vector in macaques. It also concludes that StarGen was safe and well tolerated in long-term rabbit and macaque studies. These findings support the claim in an ocular, preclinical setting, but do not establish that lentiviruses generally are safe or specify how long effective transduction was sustained. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe non-pathogenic equine infectious anemia virus (EIAV) is in clinical trials to treat Usher Syndrome and Stargardt disease.
“Currently, the non-pathogenic equine infectious anemia virus (EIAV) is in clinical trials to treat Usher Syndrome [50] and Stargardt disease [51,52].”
From The Ocular Gene Delivery Landscape (2021) · cites this paper as [51]
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- Authors
- Binley, K., Widdowson, P., Loader, J., Kelleher, M., Iqball, S., Ferrige, G., de Belin, J., Carlucci, M., Angell-Manning, D., Hurst, F., Ellis, S., Miskin, J., Fernandes, A., Wong, P., Allikmets, R., Bergstrom, C., Aaberg, T., Yan, J., Kong, J., Gouras, P., Prefontaine, A., Vezina, M., Bussieres, M., Naylor, S., & Mitrophanous, K. A.
- Affiliations
- Oxford BioMedica (United Kingdom) (GB)
- Oxford BioMedica (UK) Ltd., Oxford Science Park, Oxford, United Kingdom
- Emory University (US)
- Columbia University (US)
- Department of Ophthalmology, Emory University, Atlanta, Georgia
- Charles River Laboratories, Preclinical Services Montreal, Quebec, Canada
- Corresponding author
- Binley, Katie
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2013-06-12
- Volume
- 54
- Issue
- 6
- Pages
- 4061
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC3681475
- OpenAlex
- W2001880844
- Cited by
- 115
- References
- 31
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 7 · 2023: 5 · 2022: 9 · 2021: 12 · 2020: 5 · 2019: 8 · 2018: 8 · 2017: 12 · 2016: 13 · 2015: 15 · 2014: 11 · 2013: 2
- FWCI
- 6.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation Fighting Blindness
- Research to Prevent Blindness (EY019861)
- Sanofi
- National Institutes of Health (EY019861)
- National Eye Institute (R24EY019861, R01EY021163)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- equine infectious anemia virus, lentiviral vectors, Stargardt disease, ABCA4, subretinal gene therapy, photoreceptors, macular dystrophy, vector safety, tissue distribution, immunogenicity, ocular inflammation, macaque, rabbits
- MeSH terms
- Stargardt Disease, Animals, Body Fluids, Cytomegalovirus, Electroretinography, Enzyme-Linked Immunosorbent Assay, Infectious Anemia Virus, Equine, Female, Genetic Vectors, Intraocular Pressure, Macaca mulatta, Macular Degeneration, Male, Rabbits, Tissue Distribution, Transduction, Genetic, Transfection, Blotting, Western, Genetic Therapy, Gene Expression, Polymerase Chain Reaction, ATP-Binding Cassette Transporters, Photoreceptor Cells, Vertebrate, Green Fluorescent Proteins
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