Gene editing for inherited retinopathies - Newcells

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Gene editing for inherited retinopathies

Gene editing for inherited retinopathies using tools such as the CRIPSR-Cas 9 system, has revolutionised genome engineering and opened up more avenues for treatments.

This is particularly true for inherited retinopathies such as retinitis pigmentosa, 30-40% of which are caused by an autosomal dominant mutation. With only one copy of the gene presenting a mutation, one could envisage precision editing, particularly in the eye, an organ easily accessible.   

The main hurdle is not the technology but the lack of suitable disease models to evaluate the efficacy and safety of such a treatment. The retinal organoids and companion RPE can be derived from patients’ iPSC for disease modelling and present a powerful tool to elucidate the molecular mechanism of disease and to demonstrate the feasibly of gene editing in this in vitro model.  

Gene editing for inherited retinopathies using CRISPR-Cas 9 was used to correct the mutation in pre-mRNA processing factor 31 (PRPF31) in RP type11 patient-derived iPSCs. These organoids displayed a dysfunctional RPE, disrupted cilia morphology in photoreceptors and progressive cellular degeneration and cellular stress. Successful CRISPR-Cas 9 editing of the mutation in the PRPF31 gene resulted in the rescue of the disease phenotype, with recovery of the length and number of cilia in photoreceptors.

Gene editing for inherited retinopathies model: The human retinal organoids derived from retinitis pigmentosa type 11 patients’ (PR11) iPSCs have been successfully edited by genetic engineering using CRISPR-Cas 9.  

Restored phenotype of the cilia length, number and shape in gene-edited retinal organoids.

This work and expertise was established in Newcells Biotech co-founder’s lab Prof. Lako
Professor of Stem Cell Sciences, Biosciences Institute, Faculty of Medical Sciences,
Newcastle University

References for the page

Buskin, A. et al., Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa. Nat Commun. 2018 Oct 12;9(1):4234. doi: 10.1038/s41467-018-06448-y.

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