2′-O,4′-C-ethylene-bridged nucleic acids (ENA): highly nuclease-resistant and thermodynamically stable oligonucleotides for antisense drug

Nuclease resistant methylphosphonate-DNA/LNA chimeric oligonucleotides

“…The reactions were stopped by addition of 1 lL of a solution containing formamide and EDTA to a 1 lL sample of the reaction mixture, and the reaction products were analyzed by denaturing PAGE (20%). Although improvement in the stability towards 3 0 -exonuclease degradation by introduction of LNA into a DNA strand has been reported, 16,39,40 we here observed complete and rapid degradation of all-DNA ON1 and LNA-modified ON2 (Fig. 2).…”

2'-O,4'-C-Ethylene-Bridged Nucleic Acids (ENA) as Next-Generation Antisense and Antigene Agents

“…13,14) The conformational analysis of 2Ј-O,4Ј-C-ethylene nucleosides by 1 H-NMR has shown that in all 2Ј-O,4Ј-C-ethylene nucleosides, the coupling constant (J H1Ј-H2Ј ) was 0 Hz, which was identical to that of 2Ј-O,4Ј-Cmethylene nucleosides. 14) This means that the furanose puckering of 2Ј-O,4Ј-C-ethylene nucleosides are all fixed in the C3Ј-endo conformation (Fig.…”

“…13,14) The stability of an oligonucleotide modified with an ENA residue is identical to that of an oligonucleotide with a PS Rp diastereomer. An oligonucleotide containing two ENA residues at the 3Ј end is more stable than an oligonucleotide with a PS Sp diastereomer, which is known to be a stable isomer.…”

“…[13][14][15] They also exhibit much higher nuclease-resistance than 2Ј,4Ј-BNA/LNA. [13][14][15] Here, we review the properties of 2Ј-O,4Ј-C-ethylenebridged nucleic acids (ENA) having 2Ј-O,4Ј-C-ethylene nucleosides and the application of their oligonucleotides for use as antisense and antigene oligonucleotides.…”

AON-Mediated Exon Skipping for Duchenne Muscular Dystrophy

“…They have similar properties to LNAs, but have a higher affinity to RNA, are very stable and more nuclease-resistant (Morita et al, 2002;Yagi et al, 2004).…”