CRISPR DNA Base Editing Strategies for Treating Retinitis Pigmentosa Caused by Mutations in .

Retinitis pigmentosa (RP) is the most common group of inherited retinal degenerations and pathogenic variants in the () gene are major cause for autosomal dominant RP (adRP). Despite extensive attempts to treat -associated adRP, standardized curative treatment is still lacking. Recently developed base editors offer an exciting opportunity to correct pathogenic single nucleotide variants and are currently able to correct all transition variants and some transversion variants. In this study, we analyzed previously reported pathogenic variants ( = 247) for suitable PAM sites for currently available base editors utilizing the Cas9 (SpCas9), Cas9 (SaCas9) or the KKH variant of SaCas9 (KKH-SaCas9) to assess DNA base editing as a treatment option for -associated adRP. As a result, 55% of all the analyzed variants could, in theory, be corrected with base editors, however, PAM sites were available for only 32% of them and unwanted bystander edits were predicted for the majority of the designed guide RNAs. As a conclusion, base editing offers exciting possibilities to treat -associated adRP in the future, but further research is needed to develop base editing constructs that will provide available PAM sites for more variants and that will not introduce potentially harmful bystander edits.