ArticleHuman molecular genetics2016
In vitro and in vivo rescue of aberrant splicing in CEP290-associated LCA by antisense oligonucleotide delivery.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 108 citations in OpenAlex.
- Precision Medicine in Inherited Retinal Disease: Advances, Challenges, and Future Directions.Journal of personalized medicine · 2026Review
- Beyond the Exome: The Role of Noncoding and Regulatory Variants in Monogenic Diseases.Current issues in molecular biology · 2025Review
- Splice-modulating antisense oligonucleotides targeting a pathogenic intronic variant in adult polyglucosan body disease correct mis-splicing and restore enzyme activity in patient cells.Nucleic acids research · 2025Article
- New genetic diagnoses for inherited retinal dystrophies by integrating splicing tools into NGS pipelines.NPJ genomic medicine · 2025Article
- Adeno-Associated Virus Vectors in Retinal Gene Therapy: Challenges, Innovations, and Future Directions.Biomolecules · 2025Review
- Senior-Loken Syndrome: Ocular Perspectives on Genetics, Pathogenesis, and Management.Biomolecules · 2025Review
- Moderate levels of folic acid benefit outcomes for cilia based neural tube defects.Developmental biology · 2025Article
- Exploring non-coding variants and evaluation of antisense oligonucleotides for splicing redirection in Usher syndrome.Molecular therapy. Nucleic acids · 2024Article
- Lipopeptide-mediated Cas9 RNP delivery: A promising broad therapeutic strategy for safely removing deep-intronic variants inMolecular therapy. Nucleic acids · 2024Article
- Expanding the Clinical Spectrum ofGenes · 2024Article
- Article
- Efficacy, biodistribution and safety comparison of chemically modified antisense oligonucleotides in the retina.Nucleic acids research · 2024Article
- Lipid nanoparticle technology-mediated therapeutic gene manipulation in the eyes.Molecular therapy. Nucleic acids · 2024Review
- A Precision Therapy Approach for Retinitis Pigmentosa 11 Using Splice-Switching Antisense Oligonucleotides to Restore the Open Reading Frame of PRPF31.International journal of molecular sciences · 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
- Publication trends of Leber congenital amaurosis researches: a bibliometric study during 2002-2022.International journal of ophthalmology · 2024Article
- Experimental Model Systems Used in the Preclinical Development of Nucleic Acid Therapeutics.Nucleic acid therapeutics · 2023Article
- Clinical and Molecular Aspects of C2orf71/PCARE in Retinal Diseases.International journal of molecular sciences · 2023Review
- Detailed analysis of an enriched deep intronic ABCA4 variant in Irish Stargardt disease patients.Scientific reports · 2023Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
Leber congenital amaurosis (LCA) is a severe disorder resulting in visual impairment usually starting in the first year of life. The most frequent genetic cause of LCA is an intronic mutation in CEP290 (c.2991 + 1655A > G) that creates a cryptic splice donor site resulting in the insertion of a pseudoexon (exon X) into CEP290 mRNA. Previously, we showed that naked antisense oligonucleotides (AONs) effectively restored normal CEP290 splicing in patient-derived lymphoblastoid cells. We here explore the therapeutic potential of naked and adeno-associated virus (AAV)-packaged AONs in vitro and in vivo In both cases, AON delivery fully restored CEP290 pre-mRNA splicing, significantly increased CEP290 protein levels and rescued a ciliary phenotype present in patient-derived fibroblast cells. Moreover, administration of naked and AAV-packaged AONs to the retina of a humanized mutant Cep290 mouse model, carrying the intronic mutation, showed a statistically significant reduction of exon X-containing Cep290 transcripts, without compromising the retinal structure. Together, our data highlight the tremendous therapeutic prospective of AONs for the treatment of not only CEP290-associated LCA but potentially many other subtypes of retinal dystrophy caused by splicing mutations.
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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.