Related Experiment Video
Updated: Mar 2, 2026
Efficient PAM-Less Base Editing for Zebrafish Modeling of Human Genetic Disease with zSpRY-ABE8e
Published on: February 17, 2023
Precise and efficient DNA base editing restores normal hearing in adult DFNB9 mouse model.
Ziyu Zhang1, Man Wang1, Fangzhi Tan1
1Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China.
Gene editing successfully restored hearing in OTOF-deficient mice, demonstrating a broad therapeutic window for treating DFNB9 hearing loss. This adenine base editor approach shows promise for future gene therapies.
Area of Science:
- Genetics
- Ophthalmology
- Neuroscience
Background:
- Mutations in the OTOF gene cause autosomal recessive non-syndromic hearing loss (DFNB9), a primary cause of auditory neuropathy.
- While gene augmentation has been used in DFNB9 patients, the optimal treatment timing remains unclear.
Purpose of the Study:
- To identify an optimal adenine base editor for correcting the OTOF c.2815C>T mutation.
- To evaluate the efficacy and safety of adenine base editor-mediated gene therapy for DFNB9 in a mouse model and determine the therapeutic time window.
Main Methods:
- Screened adenine base editors to find one effective for the OTOF mutation.
- Delivered the selected editor via adeno-associated virus to the cochlea of OTOF-deficient mice at various ages.
- Assessed auditory function and safety in treated mice and wild-type controls.
Main Results:
- Nme2ABE8e showed superior on-target editing efficiency.
- Adeno-associated virus-mediated delivery of Nme2ABE8e in adult OTOF-deficient mice restored hearing to near-normal levels for at least 6 months.
- Treatment at later ages (2-4 months) also improved hearing, indicating an extended therapeutic window with no observed ototoxicity or neurological deficits.
Conclusions:
- Nme2ABE8e is a safe and effective gene therapy tool for DFNB9.
- Patients with DFNB9 may benefit from a relatively long therapeutic window for gene therapy interventions.
