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Ocular Gene Therapy Product for Rare Disease Retinitis Pigmentosa


Retinitis Pigmentosa (RP) is a blinding eye disease characterized by progressive photoreceptor degeneration that affects over 1 million people worldwide. The X-linked form of RP (or XLRP) comprises up to 20% of this disease, with mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene accounting for 75% of X-linked retinitis pigmentosa (XLRP) and 15–20% of all inherited retinal degeneration. There are approximately 10-15,000 patients with X-linked retinitis pigmentosa in the US and 230,000 worldwide. Presently there are no effective treatments and thus is an unmet need. AAV-RPGR is a replacement therapy for treating XLRP, developed exclusively at the NEI/NIH

Product: The AAV-RPGR construct delivers a full length RPGR (ORF 15) coding sequence in an Adeno Associated Virus vector that operates off the human rhodopsin kinase promoter that functions in both rods and cones.

Developmental Stage: Pre-Clinical AAV-RPGR has been tested in a RPGR-deficient mouse model system created by Tiansen Li (PNAS, 2000). In this model, gene replacement of RPGR results in long-term electroretinogram (ERG) rescue up to 18 months. Eyes treated with a single injection of mouse or human RPGR-ORF15 vector at an optimal dose maintain the expression of RPGR-ORF15 throughout the study duration, exhibit higher electroretinogram amplitude, thicker photoreceptor layer and better targeting of opsins to outer segments compared with sham-treated eyes. Furthermore, mice that received treatment at an advanced age also show remarkable preservation of retinal structure and function. These promising results demonstrate proof-of-concept in a disease-relevant animal model which may be of therapeutic value for individuals with XLRP. NEI is seeking a partner/collaborator to translate these studies into human clinical trials and eventually for commercialization.



Rescue of Retinal structure in Rpgr-KO mice
Red: RPGR; Blue DAPI

Rescue of retinal structure in Rpgr-KO mice treated with 1 × 109 AAV8-hRPGR vector. A long-term efficacy study of gene replacement therapy for RPGR-associated retinal degeneration.

Unmet need: XLRP is a rare disease and AAV-RPGR may qualify for orphan drug designation in the US.

Intellectual Property: NEI/NIH has secured intellectual property of this technology (E-050-2015) which is available for co-development, non-exclusive/exclusive license consideration.


Mala Dutta, Ph.D.
Office of Translational Research


  1. Wu Z and Swaroop A et al. A long-term efficacy study of gene replacement therapy for RPGR-associated retinal degeneration. Hum Mol Genet. 2015 Jul 15;24(14):3956-70. doi: 10.1093/hmg/ddv134.
  2. Sun X, Li T et al. Loss of RPGR glutamylation underlies the pathogenic mechanism of retinal dystrophy caused by TTLL5 mutations. Proc Natl Acad Sci U S A. 2016 May 24;113(21):E2925-34. doi: 10.1073/pnas.1523201113.

Last updated: May 18, 2020