ArticleMolecular genetics & genomic medicine2021
Gene correction of the CLN3 c.175G>A variant in patient-derived induced pluripotent stem cells prevents pathological changes in retinal organoids.
Article in Molecular genetics & genomic medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 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
- Biomedical applications of organoids in genetic diseases.Medical review (2021) · 2025Review
- CRISPR/Cas System: A Powerful Strategy to Improve Monogenic Human Diseases as Therapeutic Delivery; Current Applications and Challenges.Current gene therapy · 2025Review
- Current Status of Clinical Trials Design and Outcomes in Retinal Gene Therapy.Cold Spring Harbor perspectives in medicine · 2024Review
- Advanced Formulation Approaches for Emerging Therapeutic Technologies.Handbook of experimental pharmacology · 2024Article
- Application of patient-derived induced pluripotent stem cells and organoids in inherited retinal diseases.Stem cell research & therapy · 2023Review
- Comprehensive Genetic Analysis Unraveled the Missing Heritability and a Founder Variant of BEST1 in a Chinese Cohort With Autosomal Recessive Bestrophinopathy.Investigative ophthalmology & visual science · 2023Article
- Review
- Early recognition of CLN3 disease facilitated by visual electrophysiology and multimodal imaging.Documenta ophthalmologica. Advances in ophthalmology · 2023Article
- Review
- Long-Term Evaluation of Retinal Morphology and Function in Rosa26-Cas9 Knock-In Mice.International journal of molecular sciences · 2023Article
- Strategies to overcome the main challenges of the use of CRISPR/Cas9 as a replacement for cancer therapy.Molecular cancer · 2022Review
- Retinal organoids as models for development and diseases.Cell regeneration (London, England) · 2021Review
- The Role of Small Molecules and Their Effect on the Molecular Mechanisms of Early Retinal Organoid Development.International journal of molecular sciences · 2021Review
- The Prospects for Retinal Organoids in Treatment of Retinal Diseases.Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations in CLN3 cause Batten disease, however non-syndromic CLN3 disease, characterized by retinal-specific degeneration, has been also described. Here, we characterized an induced pluripotent stem cell (iPSC)-derived disease model derived from a patient with non-syndromic CLN3-associated retinopathy.
methodsPatient-iPSC, carrying the 1 kb-deletion and c.175G>A variants in CLN3, coisogenic iPSC, in which the c.175G>A variant was corrected, and control iPSC were differentiated into neural retinal organoids (NRO) and cardiomyocytes. CLN3 transcripts were analyzed by Sanger sequencing. Gene expression was characterized by qPCR and western blotting. NRO were characterized by immunostaining and electron microscopy.
resultsNovel CLN3 transcripts were detected in adult human retina and control-NRO. The major transcript detected in patient-NRO displayed skipping of exons 2 and 4-9. Accumulation of subunit-C of mitochondrial ATPase (SCMAS) protein was demonstrated in patient-derived cells. Photoreceptor progenitor cells in patient-NRO displayed accumulation of peroxisomes and vacuolization of inner segments. Correction of the c.175G>A variant restored CLN3 mRNA and protein expression and prevented SCMAS and inner segment vacuolization.
conclusionOur results demonstrate the expression of novel CLN3 transcripts in human retinal tissues. The c.175G>A variant alters splicing of the CLN3 pre-mRNA, leading to features consistent with CLN3 deficiency, which were prevented by gene correction.
Indexed as
Identifiers
What OpenQuestion holds
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.