AAV-Mediated Human Prominin-1 Gene Therapy Rescues Photoreceptor Degeneration in Prominin-1 Knockout Model

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Recessive mutations in prominin-1 (PROM1) cause cone-rod dystrophy (CRD), a severe inherited retinal disease with no current treatments.
• The Prominin-1 knockout (Prom1-KO) mouse model exhibits photoreceptor defects and vision loss, mimicking human CRD.

Purpose of the Study:

• To evaluate the efficacy of gene replacement therapy for CRD caused by PROM1 mutations.
• To assess the potential of a recombinant adeno-associated virus (rAAV) vector delivering the human PROM1 gene in a Prom1-KO mouse model.

Main Methods:

• A human PROM1 gene cassette was delivered via an AAV2/Cap-C14 vector into Prom1-KO mice.
• Subretinal injections were performed, and PROM1 protein expression was analyzed.
• Photoreceptor function and survival were assessed using electroretinography and histology.

Main Results:

• Human PROM1 protein was specifically expressed in the photoreceptor outer segments of treated mice.
• Vector treatment led to improved photoreceptor function and survival.
• Therapeutic effects were observed even when treatment was initiated after disease onset.

Conclusions:

• Gene replacement therapy with AAV vectors is effective in the Prom1-KO mouse model of CRD.
• This approach shows significant clinical potential for treating patients with PROM1-associated inherited retinal diseases.