ArticleHuman molecular genetics2015
Long-term rescue of cone photoreceptor degeneration in retinitis pigmentosa 2 (RP2)-knockout mice by gene replacement therapy.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Clinical response to systemic AAV gene therapy in a large animal model of late-stage lysosomal storage disease.Gene therapy · 2026Article
- Decoding retinitis pigmentosa: molecular targets and therapy with focus on pre-mRNA splicing.Cellular and molecular life sciences : CMLS · 2025Review
- Pre-Clinical and Clinical Advances in Gene Therapy of X-Linked Retinitis Pigmentosa: Hope on the Horizon.Journal of clinical medicine · 2025Review
- Gene Therapy for Retinitis Pigmentosa: Current Challenges and New Progress.Biomolecules · 2024Review
- Rescue of cone and rod photoreceptor function in a CDHR1-model of age-related retinal degeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Disrupting the ciliary gradient of active Arl3 affects rod photoreceptor nuclear migration.eLife · 2023Article
- A Natural History Study ofJournal of clinical medicine · 2022Article
- The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision.Nature communications · 2022Article
- Update of application of olfactory ensheathing cells and stem cells/exosomes in the treatment of retinal disorders.Stem cell research & therapy · 2022Review
- Gene Therapy to the Retina and the Cochlea.Frontiers in neuroscience · 2021Review
- Modeling and Rescue of RP2 Retinitis Pigmentosa Using iPSC-Derived Retinal Organoids.Stem cell reports · 2020Article
- A Common Outer Retinal Change in Retinal Degeneration by Optical Coherence Tomography Can Be Used to Assess Outcomes of Gene Therapy.Human gene therapy · 2019Article
- Functional Genomics of the Retina to Elucidate its Construction and Deconstruction.International journal of molecular sciences · 2019Review
- Novel non-sense mutation in RP2 (c.843_844insT/p.Arg282fs) is associated with a severe phenotype of retinitis pigmentosa without evidence of primary retinal pigment epithelium involvement.BMJ case reports · 2019Article
- X-linked Retinitis Pigmentosa in Japan: Clinical and Genetic Findings in Male Patients and Female Carriers.International journal of molecular sciences · 2019Article
- Ocular Ciliopathies: Genetic and Mechanistic Insights into Developing Therapies.Current medicinal chemistry · 2019Review
- A CEP290 C-Terminal Domain Complements the Mutant CEP290 of Rd16 Mice In Trans and Rescues Retinal Degeneration.Cell reports · 2018Article
- Inherited Retinal Degenerations: Current Landscape and Knowledge Gaps.Translational vision science & technology · 2018Article
- Gene therapy for the treatment of X-linked retinitis pigmentosa.Expert opinion on orphan drugs · 2018Article
- Characterization of a novel RP2-OSTF1 interaction and its implication for actin remodelling.Journal of cell science · 2018Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Retinal neurodegenerative diseases are especially attractive targets for gene replacement therapy, which appears to be clinically effective for several monogenic diseases. X-linked forms of retinitis pigmentosa (XLRP) are relatively severe blinding disorders, resulting from progressive photoreceptor dysfunction primarily caused by mutations in RPGR or RP2 gene. With a goal to develop gene therapy for the XLRP-RP2 disease, we first performed detailed characterization of the Rp2-knockout (Rp2-KO) mice and observed early-onset cone dysfunction, which was followed by progressive cone degeneration, mimicking cone vision impairment in XLRP patients. The mice also exhibited distinct and significantly delayed falling phase of photopic b-wave of electroretinogram (ERG). Concurrently, we generated a self-complementary adeno-associated viral (AAV) vector carrying human RP2-coding sequence and demonstrated its ability to mediate stable RP2 protein expression in mouse photoreceptors. A long-term efficacy study was then conducted in Rp2-KO mice following AAV-RP2 vector administration. Preservation of cone function was achieved with a wide dose range over 18-month duration, as evidenced by photopic ERG and optomotor tests. The slower b-wave kinetics was also completely restored. Morphologically, the treatment preserved cone viability, corrected mis-trafficking of M-cone opsin and restored cone PDE6 expression. The therapeutic effect was achieved even in mice that received treatment at an advanced disease stage. The highest AAV-RP2 dose group demonstrated retinal toxicity, highlighting the importance of careful vector dosing in designing future human trials. The wide range of effective dose, a broad treatment window and long-lasting therapeutic effects should make the RP2 gene therapy attractive for clinical development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.