334. A Novel Sequence-Specific Anti-Gene LNA Molecule and Its Comparison to Tail-Clamp bisPNA

Top of pageAbstract Locked Nucleic Acids (LNA) are synthetic analogs of nucleic acids, which contain a bridging methylene carbon between the 2’ and 4’ positions of the ribose ring. In this study, we generated a novel sequence-specific anti-gene LNA molecule, which induced effective binding into DNA duplexes and potent inhibition of gene transcription in the mammalian cells (|[ge]| 90 %). By comparing the novel anti-gene LNA construct with traditional LNA oligonucleotides as well as a tail-clamp bisPNA (Peptide Nucleic Acid) directed against the same target sites, respectively, we found that the novel LNA construct had unique properties for inducing gene silencing in mammalian cells. Silencing was also seen using PNA, but at doses higher than required for saturated binding suggesting the formation of inhibitory supramolecular complexes. To our knowledge, this is the first time that in mammalian cells, gene transcription was blocked by a nucleic acid analog in a sequence-specific way using low, but saturated binding of a blocking agent. This offers a novel type of anti-gene drug, which is easy to synthesize.