Description:
This invention introduces modified peptide nucleic acids that can recognize double-stranded RNA with high strength and sequence selectivity under physiological conditions. By enabling stable triple helix formation at neutral pH, these molecules overcome limitations of traditional approaches that require acidic environments. The technology opens new possibilities for therapeutic modulation, diagnostic detection, and research tools targeting biologically important RNA structures.
Background:
Double-stranded RNA plays essential roles in gene regulation and disease, yet existing methods cannot stably recognize its sequences under physiological conditions. Traditional triple helix strategies require protonated cytosine to bind, which only occurs at acidic pH. As a result, current molecules show weak or unstable binding at normal salt, pH, and temperature, preventing their practical use in biological and medical applications where precise RNA recognition is needed.
Technology Overview:
The invention uses peptide nucleic acids that include 2-aminopyridine nucleobases to enable stable triple helix formation with double-stranded RNA at physiological pH. The higher pKa of the modified base keeps it partially positively charged, allowing strong Hoogsteen pairing with G C pairs and yielding two orders of magnitude higher binding affinity than unmodified PNAs. These modified PNAs show selective binding to RNA over DNA and can recognize complex RNA structures such as microRNA precursors.
Advantages:
• Stable triple helix formation with double-stranded RNA at physiological pH
• High affinity and strong sequence selectivity
• Selective recognition of RNA over DNA targets
• Ability to bind complex and biologically relevant RNA structures
• Greater stability due to the PNA backbone
Applications:
• Therapeutic modulation of disease related double-stranded RNA
• Diagnostic detection of RNA biomarkers
• Affinity purification of target RNA molecules
• High specificity RNA imaging probes for research and diagnostics
• Tools for studying RNA structure and function
Intellectual Property Summary:
• United States, 61/719,691, Provisional, filed 10/29/2012, converted, status yes
• United States, 14/066,006, Utility, filed 10/29/2013, patented as 10,260,089 on 4/16/2019
• United States, 15/221,021, Utility, filed 7/27/2016, patented as 10,385,100 on 8/20/2019
Stage of Development:
Prototype
Licensing Status:
This technology is available for licensing.
Licensing Potential:
Information available upon request.
Additional Information:
Information available upon request.
Inventors:
Eriks Rozners, Thomas Zengeya