Large number of patients with IRDs could be treated with base editing
A large number of patients with inherited retinal diseases could be treated with base editing, according to a study.
In this retrospective cross-sectional study, data from 179 patients with biallelic pathogenic variants of genes associated with inherited retinal degeneration were analyzed. The most common recessive genes with coding sequences not deliverable in a single adeno-associated viral vector (ABCA4, CDH23, CEP290, EYS, MYO7A, and USH2A) were examined. A total of 12,369 alleles were analyzed, of which 53% were editable variants (63.1% of alleles in ABCA4, 62.7% of alleles in CDH23, 53.8% of alleles in MYO7A, 41.6% of alleles in CEP290, 37.3% of alleles in USH2A, and 22.2% of alleles in EYS).
In a cohort of patients from Oxford University Hospitals Medical Genetics Laboratories, 76% (126 of 179) of patients had ≥1 editable allele.
The authors concluded that developing base editing therapies may have the potential to treat retinal degeneration not amenable to gene therapy
These findings, if generalized to other cohorts, provide an approach for developing base editing therapies to treat retinal degeneration not easily treated by gene therapy.
Fry LE, McClements ME, MacLaren RE. Analysis of pathogenic variants correctable with CRISPR base editing among patients with recessive inherited retinal degeneration. JAMA Ophthalmol. 2021;doi:10.1001/jamaophthalmol.2020.6418