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Methods and Compositions for Treating Genetically Linked Diseases of the Eye

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The National Eye Institute (NEI) seeks a co-development partner to co-lead a pivotal multicenter trial and commercialize its AAV-RS1 Gene Therapy for X-linked retinoschisis (XLRS).
NIH Reference Number
Product Type
  • XLRS, gene therapy, orphan indication, clinical, Sieving, eye, ophthalmological
Collaboration Opportunity
This invention is available for licensing.
Description of Technology

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.

Potential Commercial Applications

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

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

Paul A Sieving M.D., Ph.D. (NEI), Ronald Bush Avery Ph.D. (NIDCD), Yong Zeng MD (NIDCD), Peter Colosi Ph.D.

Development Stage

Bush RA, et al. Preclinical Dose Escalation Study of Intravitreal AAV-RS1 Gene Therapy in a Mouse Model of X-linked Retinoschisis: Dose-Dependent Expression and Improved Retinal Structure and Function. [PMID: 27036983]

Marangoni D, et al. Ocular and systemic safety of a recombinant AAV8 vector for X-linked retinoschisis gene therapy: GLP studies in rabbits and Rs1-KO mice.  [PMID: 27626041]

Zeng Y, et al.  Retinal Structure and Gene Therapy Outcome in Retinoschisin-Deficient Mice Assessed by Spectral-Domain Optical Coherence Tomography.  [PMID: 27409484]

Patent Status
  • U.S. Patent Issued: U.S. Patent Number 9,873,893
Therapeutic Area
Thursday, August 13, 2020