Development of molecular tools that enable modulation of gene expression through specific targeting of double stranded DNA (dsDNA), is required to accelerate gene function studies and potentially identify novel classes of therapeutic agents against diseases of genetic origin. Conventional probe technologies such as triplex forming oligonucleotides and peptide nucleic acids experience sequence limitations and low target affinity.We have recently introduced Invader LNAs (Locked Nucleic Acids) as a radically different approach towards this goal. Invader LNAs are short energetically activated DNA duplexes that are chemically modified with 'energetic hotspots' of intercalator-modified LNA monomers. Both probe strands display extraordinary thermal affinity toward DNA complements, which provides an energetic gradient for specific recognition of mixed sequence dsDNA regions.In this presentation, I will outline the Invader LNA concept, discuss biophysical characteristics of these probes, disclose results from dsDNA-recognition experiments and introduce simple functional mimics of Invader LNA.

Sequence-unrestricted targeting of double stranded DNA (dsDNA): How to "unlock" the dsDNA-targeting potential of invader LNAs

243rd National Meeting (2012)

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