ArticleMolecular therapy. Nucleic acids2020
Detailed Phenotyping and Therapeutic Strategies for Intronic ABCA4 Variants in Stargardt Disease.
Article in Molecular therapy. Nucleic acids, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 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
- [Genetic therapies for Stargardt disease].Die Ophthalmologie · 2026Review
- Current Advances and Applications of Retinal Organoids.Neuroscience bulletin · 2026Review
- Model selection in preclinical nucleic acid therapeutics research.Communications biology · 2026Review
- Exon Skipping Therapy Restores Ciliary Function in USH2A-Related Retinal Degeneration.Investigative ophthalmology & visual science · 2025Article
- Investigation of ABCA4 Missense Variants and Potential Small Molecule Rescue in Retinal Organoids.Investigative ophthalmology & visual science · 2025Article
- Progression of Atrophy as a Function of ABCA4 Variants and Age of Onset in Stargardt Disease.Investigative ophthalmology & visual science · 2025Article
- Exploring organoid and assembloid technologies: a focus on retina and brain.Expert reviews in molecular medicine · 2025Review
- Preclinical assessment of splicing modulation therapy for ABCA4 variant c.768G>T in Stargardt disease.Communications medicine · 2025Article
- ABCA4 Deep Intronic Variants Contributed to Nearly Half of Unsolved Stargardt Cases With a Milder Phenotype.Investigative ophthalmology & visual science · 2025Article
- Lipopeptide-mediated Cas9 RNP delivery: A promising broad therapeutic strategy for safely removing deep-intronic variants inMolecular therapy. Nucleic acids · 2024Article
- Demonstration of the pathogenicity of a common non-exomic mutation in ABCA4 using iPSC-derived retinal organoids and retrospective clinical data.Human molecular genetics · 2024Article
- Phototoxicity avoidance is a potential therapeutic approach for retinal dystrophy caused by EYS dysfunction.JCI insight · 2024Article
- Preclinical Development of Antisense Oligonucleotides to Rescue Aberrant Splicing Caused by an UltrarareCells · 2024Article
- Splicing defects and CRISPR-Cas9 correction in isogenic homozygous photoreceptor precursors harboring clustered deep-intronic ABCA4 variants.Molecular therapy. Nucleic acids · 2024Article
- Proof-of-concept for multiple AON delivery by a single U7snRNA vector to restore splicing defects in ABCA4.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- QR-1011 restores defective ABCA4 splicing caused by multiple severe ABCA4 variants underlying Stargardt disease.Scientific reports · 2024Article
- Generating Retinas through Guided Pluripotent Stem Cell Differentiation and Direct Somatic Cell Reprogramming.Current stem cell research & therapy · 2024Review
- Multimodal spatiotemporal phenotyping of human retinal organoid development.Nature biotechnology · 2023Article
- Stargardt disease-associated missense and synonymous ABCA4 variants result in aberrant splicing.Human molecular genetics · 2023Article
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 4 countries.
Funding
Abstract
Stargardt disease is a progressive retinal disorder caused by bi-allelic mutations in the ABCA4 gene that encodes the ATP-binding cassette, subfamily A, member 4 transporter protein. Over the past few years, we and others have identified several pathogenic variants that reside within the introns of ABCA4, including a recurrent variant in intron 36 (c.5196+1137G>A) of which the pathogenicity so far remained controversial. Detailed clinical characterization of this variant confirmed its pathogenic nature, and classified it as an allele of intermediate severity. Moreover, we discovered several additional ABCA4 variants clustering in intron 36. Several of these variants resulted in aberrant splicing of ABCA4, i.e., the inclusion of pseudoexons, while the splicing defects caused by the recurrent c.5196+1137G>A variant strongly increased upon differentiation of patient-derived induced pluripotent stem cells into retina-like cells. Finally, all splicing defects could be rescued by the administration of antisense oligonucleotides that were designed to specifically block the pseudoexon insertion, including rescue in 3D retinal organoids harboring the c.5196+1137G>A variant. Our data illustrate the importance of intronic variants in ABCA4 and expand the therapeutic possibilities for overcoming splicing defects in Stargardt disease.
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