Document Detail

Transduction of photoreceptors with equine infectious anemia virus lentiviral vectors: safety and biodistribution of StarGen for Stargardt disease.
MedLine Citation:
PMID:  23620430     Owner:  NLM     Status:  MEDLINE    
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.
Katie Binley; Peter Widdowson; Julie Loader; Michelle Kelleher; Sharifah Iqball; Georgina Ferrige; Jackie de Belin; Marie Carlucci; Diana Angell-Manning; Felicity Hurst; Scott Ellis; James Miskin; Alcides Fernandes; Paul Wong; Rando Allikmets; Christopher Bergstrom; Thomas Aaberg; Jiong Yan; Jian Kong; Peter Gouras; Annick Prefontaine; Mark Vezina; Martin Bussieres; Stuart Naylor; Kyriacos A Mitrophanous
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-06-12
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  54     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-13     Completed Date:  2013-08-14     Revised Date:  2013-12-03    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4061-71     Citation Subset:  IM    
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MeSH Terms
ATP-Binding Cassette Transporters / genetics*
Blotting, Western
Body Fluids / metabolism
Cytomegalovirus / genetics
Enzyme-Linked Immunosorbent Assay
Gene Expression
Genetic Therapy
Genetic Vectors*
Green Fluorescent Proteins / genetics
Infectious Anemia Virus, Equine / genetics*
Intraocular Pressure
Macaca mulatta
Macular Degeneration / congenital*,  genetics,  metabolism,  physiopathology
Photoreceptor Cells, Vertebrate / metabolism*
Polymerase Chain Reaction
Tissue Distribution
Transduction, Genetic*
Grant Support
R01 EY021163/EY/NEI NIH HHS; R24 EY019861/EY/NEI NIH HHS; R24 EY019861/EY/NEI NIH HHS
Reg. No./Substance:
0/ABCA4 protein, human; 147336-22-9/Green Fluorescent Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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