Trans-ocular Electric Current In Vivo Enhances AAV-Mediated Retinal Gene Transduction after Intravitreal Vector...

Area of Science:

• Ophthalmology
• Gene Therapy
• Biomedical Engineering

Background:

• Adeno-associated virus (AAV) vector gene delivery shows therapeutic promise for ocular diseases.
• Current subretinal injection methods are invasive, limit retinal coverage, and risk surgical injury.
• Intravitreal delivery is preferred for reduced invasiveness and broader retinal access, but faces poor AAV retinal penetration.

Purpose of the Study:

• To develop a less invasive method for enhancing AAV vector transduction in retinal cells.
• To overcome the barrier of poor retinal penetration of AAV vectors from the vitreous cavity.
• To evaluate the safety and efficacy of a novel electro-gene delivery approach.

Main Methods:

• A non-modified AAV vector was administered intravitreally in wild-type mice.
• A brief, low-level electric current was applied across the intact eye post-injection.
• Retinal transduction and gene expression in retinal pigment epithelium and photoreceptors were assessed.

Main Results:

• Electrically enhanced intravitreal AAV delivery significantly improved transduction of retinal pigment epithelium and photoreceptor cells.
• Sustained gene expression was observed in target retinal cells.
• The low-level electric current demonstrated no adverse effects on retinal structure or function.

Conclusions:

• A minimally invasive electro-gene delivery method enhances AAV transduction from the vitreous.
• This approach offers a safer and more effective alternative to subretinal injections for retinal gene therapy.
• The method holds potential for broad application in preclinical research and clinical ophthalmology.