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Updated: May 23, 2026
07:02
Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts
Published on: May 11, 2018
Antisense-mediated exon skipping to generate soluble receptors
A Seda Yilmaz-Elis1, J Sjef Verbeek
1Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Methods in Molecular Biology (Clifton, N.J.)
|March 29, 2012
Summary
Antisense oligonucleotides (AONs) can convert membrane-bound receptors to soluble forms, inhibiting inflammatory pathways. This strategy shows promise for treating inflammatory diseases by neutralizing cytokine bioactivity.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Soluble receptors act as competitive inhibitors of ligand binding, neutralizing bioactivity.
- Cytokines play a significant role in inflammatory diseases.
- Antisense oligonucleotide (AON)-mediated exon skipping is a method to manipulate receptor isoforms.
Purpose of the Study:
- To investigate the potential of AON-mediated exon skipping for converting transmembrane receptors into soluble isoforms.
- To explore the therapeutic application of this strategy for inflammatory conditions.
- To outline methods for testing the efficacy of AON treatment.
Main Methods:
- Antisense oligonucleotide (AON) mediated exon skipping targeting transmembrane regions.
- Deletion of exons encoding transmembrane regions from mature transcripts.
- In vitro and in vivo assessment of mRNA and protein levels of membrane-bound receptors.
Main Results:
- Successful conversion of membrane-bound cytokine receptors (TNF-α and IL-5) into soluble forms using AONs.
- Demonstrated potential for inhibiting proinflammatory pathways by favoring soluble receptor expression.
Conclusions:
- AON-mediated exon skipping is a viable strategy for generating soluble receptor isoforms.
- This approach holds therapeutic potential for inflammatory diseases driven by cytokine signaling.
- Further in vivo studies on disease models are warranted to confirm efficacy.
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