Pharmaceutical Research

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Adeno-Associated Viral Gene Therapy for Inherited Retinal Disease

  • Tuyen OngEmail author
  • Mark E. Pennesi
  • David G. Birch
  • Byron L. Lam
  • Stephen H. Tsang
Expert Review
Part of the following topical collections:
  1. Ophthalmic Drug Discovery and Development


Inherited retinal diseases (IRDs) are a group of rare, heterogenous eye disorders caused by gene mutations that result in degeneration of the retina. There are currently limited treatment options for IRDs; however, retinal gene therapy holds great promise for the treatment of different forms of inherited blindness. One such IRD for which gene therapy has shown positive initial results is choroideremia, a rare, X-linked degenerative disorder of the retina and choroid. Mutation of the CHM gene leads to an absence of functional Rab escort protein 1 (REP1), which causes retinal pigment epithelium cell death and photoreceptor degeneration. The condition presents in childhood as night blindness, followed by progressive constriction of visual fields, generally leading to vision loss in early adulthood and total blindness thereafter. A recently developed adeno-associated virus-2 (AAV2) vector construct encoding REP1 (AAV2-REP1) has been shown to deliver a functional version of the CHM gene into the retinal pigment epithelium and photoreceptor cells. Phase 1 and 2 studies of AAV2-REP1 in patients with choroideremia have produced encouraging results, suggesting that it is possible not only to slow or stop the decline in vision following treatment with AAV2-REP1, but also to improve visual acuity in some patients.


AAV2-REP1 choroideremia gene therapy retina 



Adeno-associated virus


Autosomal dominant retinitis pigmentosa


Autosomal recessive retinitis pigmentosa


Best-corrected visual acuity


Balanced salt solution


CMV enhancer-CBA promoter-rabbit β-globin splice acceptor site


Chicken β-actin


Clustered Regularly Interspersed Short Palindromic Repeats


Deoxyribonucleic acid


Endoplasmic reticulum


Early Treatment Diabetic Retinopathy Study


Golgi apparatus






Wild-type human CHM cDNA


Inherited retinal diseases


Multiplicity of infection


Optical coherence tomography


Open reading frame 15




Ras-associated binding


Rab escort protein 1


Rab escort protein 2


Retinitis pigmentosa


Retinal pigment epithelium


Retinal pigment epithelial 65-kDa protein


Retinitis pigmentosa guanosine triphosphate hydrolase regulator


RPGR-interacting protein


Standard error


Visual acuity


Woodchuck hepatitis virus posttranscriptional regulatory element




X-linked retinitis pigmentosa


Acknowledgments and Disclosures

Figure 1 images courtesy of DGB. Editorial support was provided by Rebecca Franklin of Fishawack Communications Ltd. and funded by Nightstar Therapeutics. Tuyen Ong is an employee and equity holder of Nightstar Therapeutics. Mark E. Pennesi is a consultant for AGTC, Astellas, Biogen, Editas, FFB, Gensight, Horama, Ionis, Nacuity, Nightstar Therapeutics, Ophthotech, ProQR Therapeutics, RegenexBio, Sanofi, and Spark Therapeutics, and has received clinical trial support from AGTC and Nightstar Therapeutics. His institution has received support through grant P30 EY010572 from the National Institutes of Health (Bethesda, MD), and by unrestricted departmental funding from Research to Prevent Blindness (New York, NY). David G. Birch is a consultant for Acucela, AGTC, Editas, Genentech, Ionis, Nacuity, and Nightstar Therapeutics, and has received clinical trial support from AGTC, Nightstar, Ionis, and 4D Therapeutics, and grant support through EY09076 from the National Institutes of Health (Bethesda, MD, USA) and from the Foundation Fighting Blindness. Byron L. Lam declares he has no conflict of interest. Stephen H. Tsang declares he has no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Nightstar TherapeuticsWalthamUSA
  2. 2.Casey Eye InstituteOregon Health & Science UniversityPortlandUSA
  3. 3.Retina Foundation of the SouthwestDallasUSA
  4. 4.Bascom Palmer Eye InstituteUniversity of Miami Miller School of MedicineMiamiUSA
  5. 5.Department of Ophthalmology and of Pathology and Cell BiologyColumbia UniversityNew YorkUSA

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