We synthesized thymidine derivatives of 2'-C,4'-C-ethyleneoxy-bridged 2'-deoxyribonucleic acids with an 8'-methyl group ((R)-Me-EoDNA and (S)-Me-EoDNA) and without any substituent (EoDNA). Oligonucleotides including these EoDNAs showed high hybridization abilities with complementary RNA and excellent enzymatic stabilities compared with natural DNA. Moreover, the in vitro antisense potency of ol...

Design of antisense oligonucleotides targeting any mRNA can be much more efficient when several activity-enhancing motifs are included and activity-decreasing motifs are avoided. This conclusion was made after statistical analysis of data collected from >1000 experiments with phosphorothioate-modified oligonucleotides. Highly significant positive correlation between the presence of motifs CCAC,...

K. Webbley, S. Harris, J. Bloom, C. Henson, V. Wilson, C. Hawes, D. Price, J. Haffenden Pharmaron, Inc. Purpose Antisense Oligonucleotides (ASO), continue to elicit interest as novel therapeutic agents designed to specifically and selectively inhibit the production of various disease related gene products. For efficacy to occur, the therapeutic material must reach the site of action in quantiti...

In humans, recognition of a stop codon by protein release factor eRF1 leads to release of the nascent peptide from the ribosome. Although efficient eRF1 activity is usually desirable, numerous pathologies result from eRF1 recognition of premature stop mutations in essential genes. In these cases, decreased eRF1 activity could increase readthrough of the premature stop codon, thereby making full...