Technology ID

Methods and Compositions for Treating Genetically Linked Diseases of the Eye

Lead Inventor
Sieving, Paul (NIDCD)
Bush, Ronald (NIDCD)
Zeng, Yong (NIDCD)
Colosi, Peter (NEI)
Development Stages
Clinical Phase I
Lead IC

X-linked retinoschisis (XLRS) is an inherited, monogenetic ocular disease caused by mutations in the retinoschisin (RS1) gene, resulting in the development of cystic cavities throughout the retina and leading to juvenile macular degeneration. Approximately 1:15,000 males in the US are affected, classifying the condition as an orphan indication. 

The National Eye Institute (NEI) has developed a tissue-specific gene therapy approach based upon adeno-associated virus (AAV) mediated delivery of the full coding sequence for human retinoschisin to retinal cells under the control of a retinoschisin promoter.  Delivery and expression of AAV-RS1 is a novel invention for the restoration of RS1 expression in those suffering from XLRS, presenting a potential cure to an untreatable disease.  Restoration of both structure and function was demonstrated in a preclinical mouse model. A single site Phase I/IIa clinical trial of AAV-RS1 using GMP-grade material is in progress at the NIH/NEI.  

This technology will be of interest and value to licensors or co-development partners capable of evaluating the clinical and regulatory path, apply its regulatory, manufacturing, and clinical expertise in gene therapy. The licensors/collaborator will identify an optimal course toward regulatory approval in the US and other countries. Ideally, the collaborator will participate in conducting aPhase II/III multicenter trial including U.S. and European trial sites – will the submission of a BLA or comparable application for marketing approval in the US as well as relevant global markets.

Competitive Advantages:

  • Clinical-stage asset
  • No FDA approved drug or therapy is available for XLRS
  • The XLRS gene replacement strategy is applicable to all XLRS causative gene defects
  • The use of a low-seroprevalence, non-pathogenic AAV8 vector favors efficacy in a high percentage of the patient population
  • The use of a tissue specific promoter limits non-specific gene expression
  • Demonstrated GMP manufacturing process
  • Eligible for Orphan Drug Status

Commercial Applications:

Potentially curative therapy for XLRS regardless of genetic background or causative XLRS genetic defect.

Licensing Contact:
Alsaffar, Hiba