[Correction of the pathogenic mutation in the deafness gene SLC26A4 via prime editor and adenine base editor in vitro].

Objective: To investigate the feasibility of in vitro prime editor (PE) and adenine base editor (ABE) for correction the pathogenic variant of the human deafness gene SLC26A4 c.1229C>T. Methods: From March 2023 to April 2024, prime editing guide RNA (pegRNA) expression vectors as well as single guide RNA (sgRNA) were designed and constructed for the SLC26A4 c.1229C>T variant, and the feasibility of correction was performed in the HEK293T mutation model, the correction efficiency was analyzed by deep sequencing. Results: A mutant cell model of SLC26A4 c.1229C>T was successfully established. Correction was achieved in the SLC26A4 c.1229C>T mutant cell model using PE and ABE8e. Deep sequencing analysis revealed the correction efficiencies of (31.89±0.77)% and (41.07±2.28)%, respectively. Conclusion: In this study, a new base correction strategy based on the human deafness gene SLC26A4 is proposed, which provides a viable reference for gene therapy of deafness caused by SLC26A4 gene mutation.