Off-the-shelf hypoimmunogenic photoreceptors for treatment of blinding retinal disease

点击翻译按钮获取中文摘要

Blindness represents an increasing global problem with socio-economic impacts for the patients and society in general. Degenerative retinal diseases account for approximately 26% of global blindness affecting ~ 34 million people in the EU. Gene therapy, optogenetic tools, photosensitive switches and retinal prostheses have shown promising outcomes for restoring vision, but these are high-cost therapies applicable only to a small number of patients. The eye is suitable for transplantation so replacing dysfunctional photoreceptors should be feasible as long as sources of such cells are readily available. Pluripotent stem cells (PSCs) can generate cone and rod photoreceptors, which are able to integrate into the host retina and rescue vision in pre-clinical models of advanced retinal degeneration, but efficient long-term integration of allogeneic PSC-derived photoreceptors is impeded by the host immune response. To overcome this barrier and make this treatment accessible to a large number of patients with photoreceptor degeneration, I propose to: (1) generate off-the-shelf, immune-transparent (hypoimmunogenic) PSC-derived photoreceptors; (2) assess their effectiveness in evading the host immune system and (3) determine their long-term integration and ability to restore vision in pre-clinical models of advanced retinal degeneration. This novel high-gain approach provides a game-changing, effective and scalable photoreceptor transplantation platform, and a much-needed paradigm shift that will improve the quality of life for the millions of sufferers with blinding retinal disease. Through my involvement in successful phase I/II clinical trials of reversing corneal blindness via transplantation of limbal stem cells, I have had a unique opportunity to translate my research findings into treatments for patients with this rare disease. I now aim to build and validate a novel cell transplantation platform that will revolutionise the treatment of retinal degeneration.