Gene therapy for PRPH2-associated ocular disease: challenges and prospects

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• The peripherin-2 (PRPH2) gene is essential for photoreceptor outer segment structure and function.
• Mutations in PRPH2 cause inherited retinal diseases like retinitis pigmentosa and macular degeneration.
• Over 90 disease-causing PRPH2 mutations are known, highlighting significant genetic heterogeneity.

Purpose of the Study:

• To review the progress and prospects of gene therapy for PRPH2-associated retinal disorders.
• To discuss the challenges and potential solutions for developing clinically viable PRPH2 gene therapies.

Main Methods:

• Review of preclinical gene therapy studies utilizing adeno-associated viruses and DNA nanoparticles.
• Analysis of pathogenic mechanisms and dosage requirements for PRPH2 gene replacement.

Main Results:

• Successful preclinical gene therapy in mouse models (rds(-/-) and rds(+/-)) demonstrates proof-of-concept.
• Complexities in disease mechanisms and the need for precise therapeutic dosing are identified as hurdles.

Conclusions:

• PRPH2 gene therapy holds therapeutic potential for inherited retinal diseases.
• Overcoming challenges in pathogenic understanding and precise dose delivery is crucial for clinical success.