ArticleMolecular therapy. Nucleic acids2019
Combining Engineered U1 snRNA and Antisense Oligonucleotides to Improve the Treatment of a BBS1 Splice Site Mutation.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Bardet-Biedl syndrome 1 mutations differentially impact BBSome integrity and ciliary trafficking.Cell communication and signaling : CCS · 2026Article
- Article
- Extracellular Vesicle-Mediated U1 snRNA Delivery Restores Aberrant Pre-mRNA Splicing in Human Cells.Biomolecules · 2026Article
- Clinical heterogeneity associated with Bardet-Biedl syndrome-related genes in presumed non-syndromic inherited retinal disease.Frontiers in cell and developmental biology · 2026Article
- RNA dysfunction in age-related macular degeneration: the role of U1 snRNP complex and neurodegenerative diseases.International journal of retina and vitreous · 2025Review
- Molecular treatment options for patients carryingMolecular therapy. Nucleic acids · 2025Article
- Molecular Consequences of a Missense PHF21A Variant, c.1285G > A, Associated With Syndromic Neurodevelopmental Disorder.Cellular and molecular neurobiology · 2025Article
- Splicing Modulation via Antisense Oligonucleotides in Recessive Dystrophic Epidermolysis Bullosa.International journal of molecular sciences · 2024Article
- Characterization and Engineered U1 snRNA Rescue of Splicing Variants in a Turkish Neurodevelopmental Disease Cohort.Human mutation · 2024Article
- Development of Engineered-U1 snRNA Therapies: Current Status.International journal of molecular sciences · 2023Review
- Article
- Counteracting the Common Shwachman-Diamond Syndrome-CausingInternational journal of molecular sciences · 2023Article
- Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example.Life (Basel, Switzerland) · 2022Review
- How to Design U1 snRNA Molecules for Splicing Rescue.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Autosomal dominant optic atrophy: A novel treatment forMolecular therapy. Nucleic acids · 2021Article
- Bardet-Biedl syndrome-7 (Ophthalmic genetics · 2021Article
- Profiling of cis- and trans-acting factors supporting noncanonical splice site activation.RNA biology · 2021Article
- U5 snRNA Interactions With Exons Ensure Splicing Precision.Frontiers in genetics · 2021Article
- Combined Treatment with Peptide-Conjugated Phosphorodiamidate Morpholino Oligomer-PPMO and AAV-U7 Rescues the Severe DMD Phenotype in Mice.Molecular therapy. Methods & clinical development · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Manipulation of pre-mRNA processing is a promising approach toward overcoming disease-causing mutations and treating human diseases. We show that a combined treatment applying two splice-manipulating technologies improves therapeutic efficacies to correct mutation-induced splice defects. Previously, we identified a family affected by retinitis pigmentosa caused by the homozygous BBS1 splice donor site mutation c.479G > A. The mutation leads to both exon 5 skipping and intron 5 retention. We developed a therapeutic approach applying lentivirus-mediated gene delivery of engineered U1 small nuclear RNA (U1), which resulted in increased levels of correctly spliced BBS1. Herein, we show that the therapeutic effect of the engineered U1 efficiently reverted exon skipping but failed to reduce the intron retention. To complement the engineered U1 treatment, we identified four different antisense oligonucleotides (AONs) that block intron 5 retention in BBS1 transcripts. A treatment using engineered U1 in combination with AONs showed the highest therapeutic efficacy and increased the amount of correctly spliced BBS1 transcripts. We did not detect elevated levels of apoptotic cell death in AON-treated cell lines. In conclusion, engineered U1 or AONs provide efficient therapies with complementary effects and can be combined to increase efficacy of therapeutic approaches to correct splice defects.
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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.