Synthetic LNA/DNA Nano-scaffolds for Highly Efficient Diagnostics of Nucleic Acids and Autoimmune Antibodies

I.K. Astakhova
University of Southern Denmark, DK

Keywords: diagnostics, nanotechnology, antibody, oligonucleotide

Summary:

Herein we describe fluorescent oligonucleotides prepared by click chemistry between novel alkyne-modified locked nucleic acid (LNA) strands and a series of fluorescent azides for highly efficient homogeneous (all-in-solution) detection of nucleic acids and autoimmune antibodies. The click approach presented here efficiently yields probes with various dyes attached internally at the 2′-amino-position of 2′-amino-LNA scaffolds. This approach provides a reliable foundation for simple and efficient preparation of a library of fluorescent LNA/DNA nano-scaffolds, screening and indication of several bright oligonucleotides with high target binding affinity and specificity for diagnostic purposes. As demonstrated by our studies, potential applications of these scaffolds include a wide range of fluorescence assays including, but not limited to, live-cell nucleic acid imaging, aptasensing and nucleic acid diagnostics. Moreover, the 2′-N-alkynyl group in the LNA/DNA strands is available for the attachment of other tags such as carbohydrates, lipids, cofactors and cell-penetrating peptides. In this context we believe that “clickable” LNA/DNA probes offer appealing opportunities for developing efficient tools for biosensing, pharmacological or nano-production purposes.