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Scott Ellis, James Miskin, Katie Binley, Jackie de Belin, Julie Loader, Michelle Kelleher, Stuart Naylor, Kyriacos Mitrophanous; LentiVector® Platform, a Highly Effective Equine Infectious Anaemia Virus-based Lentiviral Gene Therapy Platform for Ocular Disease. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1912.
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Oxford BioMedica has developed ocular gene therapies using its proprietary LentiVector® platform which is based on recombinant Equine Infectious Anaemia Virus (EIAV). Currently we have four ocular therapies: RetinoStat®, StarGen™, UshStat® and EncorStat®, for the treatment of age-related macular degeneration, Stargardt macula dystrophy, Usher Syndrome 1B, and the prevention of corneal transplant rejection respectively. RetinoStat®, StarGen™ and UshStat® have received regulatory approval in the US and France (IND/CTA) and are currently in clinical evaluation. The development of lentiviral vector-based gene therapies to treat eye diseases is an attractive option due to the vector’s innate ability to express therapeutic genes for extended periods, either to correct inherited disease, or to interfere with disease aetiology. The accessibility of the eye both for administration and evaluating therapeutic benefit, combined with the anatomical separation from the rest of the body preventing spread of the vector, are also significant advantages.
The LentiVector® platform has been extensively characterized in GLP safety and biodistribution studies following subretinal administration, as part of the RetinoStat®, StarGen™ and UshStat® programmes. These studies were conducted in rabbits and NHP for up to 6 month duration.
Subretinal administration of all three products caused only mild-to-moderate ocular inflammation (in the absence of prophylactic anti-inflammatory medication) that was transient, completely resolving within 1 month. Subretinal administration of vector caused no long-term detrimental changes within the eye. Biodistribution studies of vector demonstrated that the lentiviral vector products did not escape the ocular compartment, and as a result little or no antibody responses were observed in these studies.
The EIAV-based LentiVector® platform has been shown to be an effective and safe system for the delivery of relatively large genes into target retinal cells resulting in stable and long-term therapeutic expression.
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