ArticleCommunications medicine2025
Preclinical assessment of splicing modulation therapy for ABCA4 variant c.768G>T in Stargardt disease.
Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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
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Who cites it
4 citing papers in PubMed.
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- To scramble or not: Steric blocking 2'-MOE/PS control antisense oligonucleotides across cellular models.Molecular therapy. Nucleic acids · 2026Article
- Organoids for Metabolic Disease Modeling.Journal of inherited metabolic disease · 2026Review
- Investigation of ABCA4 Missense Variants and Potential Small Molecule Rescue in Retinal Organoids.Investigative ophthalmology & visual science · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
backgroundStargardt disease type 1 (STGD1) is a progressive retinal disorder caused by bi-allelic variants in the ABCA4 gene. A recurrent variant at the exon-intron junction of exon 6, c.768G>T, causes a 35-nt elongation of exon 6 that leads to premature termination of protein synthesis.
methodsTo correct this aberrant splicing, twenty-five 2'-O-methoxyethyl antisense oligonucleotides (AONs) were designed, spanning the entire exon elongation.
resultsTesting of these AONs in patient-derived photoreceptor precursor cells and retinal organoids allow the selection of a lead candidate AON (A7 21-mer) that rescues on average 52% and 50% expression of wild-type ABCA4 transcript and protein, respectively. In situ hybridization and probe-based ELISA demonstrate its distribution and stability in vitro and in vivo. No major safety concerns regarding off-targets, immunostimulation and toxicity are observed in transcriptomics analysis, cytokine stimulation assays in human primary immune cells, and cytotoxicity assays.
conclusionsAdditional optimization and in vivo studies will be performed to further investigate the lead candidate. Considering the high prevalence of this variant, a substantial number of patients are likely to benefit from a successful further development and implementation of this therapy.
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Registered trials
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