ArticleMolecular therapy. Nucleic acids2018
Splice-Modulating Oligonucleotide QR-110 Restores CEP290 mRNA and Function in Human c.2991+1655A>G LCA10 Models.
Article in Molecular therapy. Nucleic acids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 2 of them syntheses 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
107 citing papers in PubMed, 2 syntheses or guidelines pooled it, 163 citations in OpenAlex.
- Retinal Organoids from Induced Pluripotent Stem Cells of Patients with Inherited Retinal Diseases: A Systematic Review.Stem cell reviews and reports · 2025Pooled it
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial.Nature medicine · 2022Trial
- Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect.Nature medicine · 2019Trial
- To scramble or not: Steric blocking 2'-MOE/PS control antisense oligonucleotides across cellular models.Molecular therapy. Nucleic acids · 2026Article
- Antisense oligonucleotide allele-specific targeting of EFEMP1 in a patient-derived model of Doyne honeycomb retinal dystrophy.Molecular therapy. Nucleic acids · 2026Article
- Engineering Human Retinal Organoids and Eye-on-a-Chip Models for Degenerative Eye Disease.ACS biomaterials science & engineering · 2026Review
- Review
- Beyond the Exome: The Role of Noncoding and Regulatory Variants in Monogenic Diseases.Current issues in molecular biology · 2025Review
- Retinal organoids mirror CRISPR-Cas9 gene editing efficiency observedMolecular therapy. Methods & clinical development · 2025Article
- Therapeutic antisense oligonucleotide mitigates retinal dysfunction in a pig model of CLN3 Batten disease.Nucleic acids research · 2025Article
- Molecular treatment options for patients carryingMolecular therapy. Nucleic acids · 2025Article
- Exon Skipping Therapy Restores Ciliary Function in USH2A-Related Retinal Degeneration.Investigative ophthalmology & visual science · 2025Article
- Retinal Organoids: Innovative Tools for Understanding Retinal Degeneration.International journal of molecular sciences · 2025Review
- Unveiling sequence-agnostic mixed-chemical modification patterns for splice-switching oligonucleotides using the NATURA platform.Molecular therapy. Nucleic acids · 2025Article
- PathogeniciScience · 2025Article
- Comparison of CRISPR-Cas13b RNA base editing approaches for USH2A-associated inherited retinal degeneration.Communications biology · 2025Article
- Identification of deep intronic variants in junctional epidermolysis bullosa using genome sequencing and splicing assays.NPJ genomic medicine · 2025Article
- Non-viral gene therapy for Leber's congenital amaurosis: progress and possibilities.Nanomedicine (London, England) · 2025Review
- Preclinical assessment of splicing modulation therapy for ABCA4 variant c.768G>T in Stargardt disease.Communications medicine · 2025Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Leber congenital amaurosis type 10 (LCA10) is a severe inherited retinal dystrophy associated with mutations in CEP290. The deep intronic c.2991+1655A>G mutation in CEP290 is the most common mutation in LCA10 individuals and represents an ideal target for oligonucleotide therapeutics. Here, a panel of antisense oligonucleotides was designed to correct the splicing defect associated with the mutation and screened for efficacy and safety. This identified QR-110 as the best-performing molecule. QR-110 restored wild-type CEP290 mRNA and protein expression levels in CEP290 c.2991+1655A>G homozygous and compound heterozygous LCA10 primary fibroblasts. Furthermore, in homozygous three-dimensional iPSC-derived retinal organoids, QR-110 showed a dose-dependent restoration of mRNA and protein function, as measured by percentage and length of photoreceptor cilia, without off-target effects. Localization studies in wild-type mice and rabbits showed that QR-110 readily reached all retinal layers, with an estimated half-life of 58 days. It was well tolerated following intravitreal injection in monkeys. In conclusion, the pharmacodynamic, pharmacokinetic, and safety properties make QR-110 a promising candidate for treating LCA10, and clinical development is currently ongoing.
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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.