Towards in vivo genome editing of post-mitotic mammalian photoreceptors for treatment of Inherited Retinal Dystrophies (360G-Wellcome-215343_Z_19_Z)
Retinitis Pigmentosa (RP) causes untreatable visual loss. Gene augmentation trials for genetic eye disease have disappointed, partly due to difficulties in optimising correct, persistent exogenous gene expression. The possibility of precise, efficient gene correction using genome editing technology for highly genetically heterogenous diseases like RP would overcome these dosage issues. To determine the feasibility of genome editing, we have developed powerful fluorescent reporter mouse models, allowing sensitive readouts of editing events in time and space. Using these, we demonstrated post-natal murine photoreceptors are amenable to genome editing in retinal explants. However, several obstacles exist to making editing a reality in the disease setting. This project aims to: optimise targeted editing machinery delivery to photoreceptors in vivo; improve photoreceptor repair efficiency; explore novel, homology-independent strategies for photoreceptor gene correction; assess potential for editing technology to rescue vision. To expedite solutions, we propose using our reporter models to develop in vivo photoreceptor editing. We have prepared retinotrophic AAV serotypes containing machinery necessary to edit our models. Following optimisation in reporter models, we will assess repair of disease-causing mutations in our humanised mouse RP models. These experiments will provide vital pilot data towards securing industrial partnerships to translate this technology into clinic.
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Grant Details
Amount Awarded | 98979 |
Applicant Surname | Megaw |
Approval Committee | Science Seeds Advisory Panel |
Award Date | 2018-11-02T00:00:00+00:00 |
Financial Year | 2018/19 |
Grant Programme: Title | Seed Award in Science |
Internal ID | 215343/Z/19/Z |
Lead Applicant | Dr Roly Megaw |
Partnership Value | 98979 |
Planned Dates: End Date | 2021-10-01T00:00:00+00:00 |
Planned Dates: Start Date | 2019-04-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Scotland |