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High-affinity RNA ligands to basic fibroblast growth factor inhibit receptor binding
D Jellinek1, C K Lynott, D B Rifkin
1NeXagen, Inc., Boulder, CO 80301.
Summary
Researchers discovered specific RNA ligands that bind to basic fibroblast growth factor, inhibiting its receptor binding and signaling pathway. This highlights the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method for creating targeted oligonucleotide antagonists.
Area of Science:
- Molecular Biology
- Biochemistry
- Drug Discovery
Background:
- Basic fibroblast growth factor (FGF2) is crucial in cellular processes.
- Understanding FGF2 signaling is key for therapeutic development.
- Targeted inhibition of FGF2 offers potential therapeutic strategies.
Purpose of the Study:
- To isolate high-affinity, specific RNA ligands for basic fibroblast growth factor.
- To characterize the binding properties and inhibitory potential of these RNA ligands.
- To demonstrate the utility of SELEX for discovering oligonucleotide antagonists.
Main Methods:
- Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was employed.
- A large pool of RNA molecules (10^14) with randomized sequences was screened.
- Binding affinity, specificity, and functional inhibition assays were performed.
Main Results:
- RNA ligands with low-nanomolar affinity and high specificity for FGF2 were isolated.
- Ligands were classified into two families based on sequence and structure.
- These RNA ligands inhibited FGF2 binding to its cell-surface receptors.
Conclusions:
- SELEX is an effective method for discovering potent RNA antagonists.
- Isolated RNA ligands can block FGF2-mediated signaling.
- These findings pave the way for novel FGF2-targeted therapies.