Cited by 147Retinal Development and DisordersVirus-based gene therapy researchRNA Interference and Gene Delivery

Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector

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Cideciyan, Artur V., Sudharsan, Raghavi, Dufour, Valérie L., Massengill, Michael T., Iwabe, Simone, Swider, Malgorzata, Lisi, Brianna, Sumaroka, Alexander +8 more·2018·Proceedings of the National Academy of Sciences

Abstract

Significance A number of gene-augmentation strategies are entering clinical trials for the treatment of inherited retinal blindness. Gene therapy for autosomal dominant diseases faces significant obstacles that include allelic heterogeneity and the potential need to silence the mutated gene. Here we show that a single-gene therapy vector that combines knockdown of the causative gene with its replacement by a resistant wild-type copy can prevent photoreceptor cell death and vision loss in a canine model of autosomal dominant retinitis pigmentosa.

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  • In a canine model of RHO-associated retinitis pigmentosa, this vector preserved retinal structure and function for up to 8 months.

    “This gene therapy vector has been tested in a canine model of RHO-associated retinitis pigmentosa, which showed preservation of retinal structure and function up to 8-months follow-up.”

    From Correcting visual loss by genetics and prosthetics (2020) · cites this paper as Cideciyan 2018

  • Cideciyan et al. built an AAV vector that delivers an shRNA to silence endogenous RHO while providing a codon-modified wild-type RHO that resists RNA interference.

    “Cideciyan et al. constructed an AAV vectors which delivers a short hairpin RNA (shRNA) that silences endogenous RHO gene expression while introducing a codon-modified version of wild-type RHO that is resistant to the RNA interference [Cideciyan 2018].”

    From Correcting visual loss by genetics and prosthetics (2020) · cites this paper as Cideciyan 2018

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Authors
Cideciyan, A. V., Sudharsan, R., Dufour, V. L., Massengill, M. T., Iwabe, S., Swider, M., Lisi, B., Sumaroka, A., Marinho, L. F., Appelbaum, T., Rossmiller, B., Hauswirth, W. W., Jacobson, S. G., Lewin, A. S., Aguirre, G. D., & Beltran, W. A.
Affiliations
  • University of Pennsylvania (US)
  • University of Florida (US)
  • Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
  • University of Florida Health (US)
Venue
Proceedings of the National Academy of Sciences
Published
2018-08-20
Volume
115
Issue
36
Pages
E8547-E8556
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2888444358
Cited by
147
References
86
Citations by year
2026: 10 · 2025: 12 · 2024: 11 · 2023: 17 · 2022: 19 · 2021: 28 · 2020: 28 · 2019: 20 · 2018: 1
FWCI
6.85
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • HHS | NIH | National Eye Institute (R24-EY022012, R01-EY06855, P30-EY001583, P30-EY021721)
  • Foundation Fighting Blindness (C-GT-0414-0634-UPA01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
rhodopsin, gene therapy, autosomal dominant retinitis pigmentosa, adeno-associated virus vectors, gene knockdown, gene replacement, photoreceptor cell death, allelic heterogeneity, canine model, vision loss
MeSH terms
Dependovirus, Animals, Dogs, Genetic Vectors, Humans, Retinitis Pigmentosa, Rhodopsin, Genetic Therapy, RNA, Catalytic, Retinal Rod Photoreceptor Cells, Gene Knockdown Techniques, Gene Knock-In Techniques, HEK293 Cells

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