ArticleScientific reports2019
Reduction of integrin alpha 4 activity through splice modulating antisense oligonucleotides.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Expanding the toolbox: Emerging antisense oligonucleotide mechanisms for modulating gene expression.Molecular therapy. Nucleic acids · 2026Review
- Comparative transcriptome analysis provides new insights into the molecular mechanism of blunt snout bream (Megalobrama amblycephala) heart in response to hypoxic stress.Fish physiology and biochemistry · 2025Article
- Molecular Dissection of the Arsenic-Induced Leukocyte Incursion into the Inflamed Thymus and Spleen and Its Amelioration by Co-supplementation of L-Ascorbic Acid and α-Tocopherol.Biological trace element research · 2025Article
- Expansion of Splice-Switching Therapy with Antisense Oligonucleotides.International journal of molecular sciences · 2025Review
- Down syndrome and DYRK1A overexpression: relationships and future therapeutic directions.Frontiers in molecular neuroscience · 2024Review
- Induced alternative splicing an opportunity to study PCSK9 protein isoforms at physiologically relevant concentrations.Scientific reports · 2023Article
- Differing coronavirus genres alter shared host signaling pathways upon viral infection.Scientific reports · 2022Article
- Developing predictive hybridization models for phosphorothioate oligonucleotides using high-resolution melting.PloS one · 2022Article
- Polyglutamine Ataxias: Our Current Molecular Understanding and What the Future Holds for Antisense Therapies.Biomedicines · 2021Review
- Antisense Oligonucleotide-Mediated Exon-skipping Therapies: Precision Medicine Spreading from Duchenne Muscular Dystrophy.JMA journal · 2021Review
- TargetedBiomedicines · 2021Article
- Dual Fluorescence Splicing Reporter Minigene Identifies an Antisense Oligonucleotide to Skip Exon v8 of theInternational journal of molecular sciences · 2020Article
- Systematic Approach to Developing Splice Modulating Antisense Oligonucleotides.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With recent approvals of antisense oligonucleotides as therapeutics, there is an increasing interest in expanding the application of these compounds to many other diseases. Our laboratory focuses on developing therapeutic splice modulating antisense oligonucleotides to treat diseases potentially amendable to intervention during pre-mRNA processing, and here we report the use of oligomers to down-regulate integrin alpha 4 protein levels. Over one hundred antisense oligonucleotides were designed to induce skipping of individual exons of the ITGA4 transcript and thereby reducing protein expression. Integrin alpha 4-mediated activities were evaluated in human dermal fibroblasts and Jurkat cells, an immortalised human T lymphocyte cell line. Peptide conjugated phosphorodiamidate morpholino antisense oligomers targeting ITGA4 were also assessed for their effect in delaying disease progression in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. With the promising results in ameliorating disease progression, we are optimistic that the candidate oligomer may also be applicable to many other diseases associated with integrin alpha 4 mediated inflammation. This highly specific strategy to down-regulate protein expression through interfering with normal exon selection during pre-mRNA processing should be applicable to many other gene targets that undergo splicing during expression.
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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 Socratic graph.