Genome editing, a superior therapy for inherited retinal diseases

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Monogenic inherited retinal diseases are a significant cause of blindness.
• Current gene augmentation therapies face challenges like progressive degeneration and waning efficacy.
• Genome editing presents a novel therapeutic avenue with potential for permanent genetic correction.

Purpose of the Study:

• To review the applications, strengths, and drawbacks of gene augmentation for inherited retinal diseases.
• To explore recent advances in genome editing technologies for retinal disorders.
• To discuss preclinical strategies for advancing genome editing therapies in patients.

Main Methods:

• Review of gene augmentation strategies.
• Analysis of CRISPR-Cas9-based genome editing techniques (gene disruption, ablate-and-replace, base editing, prime editing).
• Evaluation of delivery modalities and safety profiles.

Main Results:

• Gene augmentation is available but has limitations.
• Genome editing offers precise DNA modification for potentially permanent correction.
• Advances in delivery improve safety and reduce off-target effects.

Conclusions:

• Genome editing technologies, including base and prime editing, offer significant advantages over traditional gene augmentation.
• Improved delivery methods enhance the safety and efficacy of genome editing for retinal diseases.
• Continued progress in genome editing and delivery strategies may establish it as the leading treatment for genetic retinal disorders.