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Published on: August 27, 2019
NFkappaB decoy oligonucleotides
Daniela De Stefano1, Giuseppe De Rosa, Rosa Carnuccio
1University of Naples Federico II, Department of Experimental Pharmacology, via D Montesano 49, 80131 Naples, Italy. dadestef@unina.it.
Abstract:
Molecular therapy is emerging as a potential strategy for the treatment of inflammatory diseases. Decoy oligonucleotides (ONs) against NFkappaB, an inducible transcription factor that plays a critical role in several inflammatory/immune diseases, can specifically block the transcriptional activity of this transcription factor. The therapeutic potential of such decoy ONs has been investigated in several chronic inflammatory-based diseases. However, the clinical use of decoy ONs is strongly hampered by several issues, including low bioavailability, a short half-life and limited intracellular uptake. Both chemical modifications to ONs and the use of delivery systems have been investigated in order to overcome these limitations. This review summarizes the most meaningful studies on the preclinical and clinical application of decoy ONs against NFkappaB in different diseases, and highlights successful strategies that have overcome the pharmacokinetic issues associated with ONs.
Insights
Decoy oligonucleotides targeting NF-kappaB show promise for inflammatory diseases. Strategies are improving their delivery and effectiveness for clinical use.
Area of Science:
- Molecular therapy
- Immunology
- Pharmacology
Background:
- Inflammatory diseases pose significant health challenges.
- NF-kappaB is a key transcription factor in inflammatory and immune responses.
- Decoy oligonucleotides (ONs) offer a targeted approach to inhibit NF-kappaB activity.
Purpose of the Study:
- To review the preclinical and clinical applications of NF-kappaB decoy ONs.
- To highlight strategies for overcoming pharmacokinetic limitations of ONs.
Main Methods:
- Review of existing scientific literature on NF-kappaB decoy ONs.
- Analysis of studies investigating chemical modifications and delivery systems for ONs.
Main Results:
- Decoy ONs effectively block NF-kappaB transcriptional activity.
- Pharmacokinetic issues like low bioavailability and short half-life limit clinical use.
- Chemical modifications and advanced delivery systems show potential to improve ON efficacy.
Conclusions:
- NF-kappaB decoy ONs represent a promising molecular therapy for inflammatory diseases.
- Overcoming pharmacokinetic challenges is crucial for successful clinical translation.
- Further research into optimized delivery systems is warranted.
