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Replies to post #683 on Oxford BioMedica PLC (OXBDF)
Last, but not least, RetinoStat has been developed to tackle retinal neovascularization, which is associated to the age-related macular degeneration. Neovascularization is quenched physiologically by the angiostatic proteins expressed during the process of normal wound healing [143]. Based on this concept, RetinoStat contains two potently angiostatic genes, endostatin and angiostatin [111]. When subretinally injected in mice, rabbits, and macaques, RetinoStat efficiently abolished the retinal blood vessel proliferation [102,108,111]. This evidence opened the way for the first phase I clinical trial testing the safety of subretinal injection of a non-primate lentiviral vector in patients affected by neovascular age-related macular degeneration [116]. This study confirmed that not only RetinoStat provides robust and sustained expression of the bicistronic transgene, but it also helps to reduce the excess fluid characteristically residing in the neural retina of sick patients [116].
A complementary non-primate lentiviral platform, named EncorStat, has been more recently developed to minimize corneal neovascularization, which represents the most important risk factor for rejection following corneal transplantation [144]. To this purpose, the bicistronic organization of EncorStat allows the delivery of the same two angiostatic proteins synthesized by Retinostat [113]. Worth mentioning, rabbit corneas incubated with EncorStat before surgery significantly suppressed neovascularization in a rabbit model of corneal rejection, favouring the improvement of an ex vivo therapeutic protocol [113].
RetinoStat and EncorStat are only two recent examples testifying that the carrying capacity of lentiviral vectors may permit co-delivery of multiple genes. This aspect is of relevant interest for future clinical application, since it could facilitate multifaceted targeting of eye disorders with potentially greater therapeutic effects than single gene delivery approaches. Furthermore, beneficial outcomes could be extended to cell types not directly transduced by lentiviral vectors if, for example, a paracrine effect could be attained by a sufficient amount of a therapeutic protein secreted by adjacent transduced cells.
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