ArticleGenes2019
Antisense Oligonucleotide-Based Downregulation of the G56R Pathogenic Variant Causing
Article in Genes, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Clinical and Genetic Features ofGenes · 2023Pooled it
- Article
- Knocking Down Long Noncoding RNAs Using Antisense Oligonucleotide Gapmers.Methods in molecular biology (Clifton, N.J.) · 2026Article
- NR2E3 inhibits the inflammation and apoptosis in diabetic retinopathy by regulating the AHR/IL-17A signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Evaluation of mesenchymal stem cells as anFrontiers in cell and developmental biology · 2024Review
- Alternative RNA Splicing in the Retina: Insights and Perspectives.Cold Spring Harbor perspectives in medicine · 2023Review
- Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3): Role in Retinal Development and Disease.Genes · 2023Review
- Disease-causing mutations in genes encoding transcription factors critical for photoreceptor development.Frontiers in molecular neuroscience · 2023Review
- Antisense oligonucleotides targeting exon 11 are able to partially rescue the NF2-related schwannomatosis phenotypeMolecular therapy. Nucleic acids · 2022Article
- Antisense RNA Therapeutics: A Brief Overview.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Molecular Therapy for Choroideremia: Pre-clinical and Clinical Progress to Date.Molecular diagnosis & therapy · 2021Article
- Nanotechnology-Based Strategies to Overcome Current Barriers in Gene Delivery.International journal of molecular sciences · 2021Review
- AON-based degradation of c.151C>T mutantMolecular therapy. Nucleic acids · 2021Article
- Allele-Specific Knockout by CRISPR/Cas to Treat Autosomal Dominant Retinitis Pigmentosa Caused by the G56R Mutation in NR2E3.International journal of molecular sciences · 2021Article
- Gene Therapy in Inherited Retinal Diseases: An Update on Current State of the Art.Frontiers in medicine · 2021Review
- Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa.Journal of clinical medicine · 2020Review
- A Review of Gene, Drug and Cell-Based Therapies for Usher Syndrome.Frontiers in cellular neuroscience · 2020Article
- Molecular Therapies for Inherited Retinal Diseases-Current Standing, Opportunities and Challenges.Genes · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The recurrent missense variant in Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3), c.166G>A, p.(Gly56Arg) or G56R, underlies 1%-2% of cases with autosomal dominant retinitis pigmentosa (adRP), a frequent, genetically heterogeneous inherited retinal disease (IRD). The mutant NR2E3 protein has a presumed dominant negative effect (DNE) by competition for dimer formation with Cone-Rod Homeobox (CRX) but with abolishment of DNA binding, acting as a repressor in trans. Both the frequency and DNE of G56R make it an interesting target for allele-specific knock-down of the mutant allele using antisense oligonucleotides (AONs), an emerging therapeutic strategy for IRD. Here, we designed gapmer AONs with or without a locked nucleic acid modification at the site of the mutation, which were analyzed for potential off-target effects. Next, we overexpressed wild type (WT) or mutant NR2E3 in RPE-1 cells, followed by AON treatment. Transcript and protein levels of WT and mutant NR2E3 were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot respectively. All AONs showed a general knock-down of mutant and WT NR2E3 on RNA and protein level, showing the accessibility of the region for AON-induced knockdown. Further modifications are needed however to increase allele-specificity. In conclusion, we propose the first proof-of-concept for AON-mediated silencing of a single nucleotide variation with a dominant negative effect as a therapeutic approach for NR2E3-associated adRP.
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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.