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

To investigate the feasibility of prime editor (PE) and adenine base editor (ABE) for correction the pathogenic variant of the human deafness gene c.1229C>T. 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 c.1229C>T variant, and the feasibility of correction was performed in the HEK293T mutation model, the correction efficiency was analyzed by deep sequencing. A mutant cell model of c.1229C>T was successfully established. Correction was achieved in the 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. In this study, a new base correction strategy based on the human deafness gene is proposed, which provides a viable reference for gene therapy of deafness caused by ene mutation.