Antisense inhibitory effect: A comparison between 3 '-partial and full phosphorothioate antisense oligonucleotides

Phosphorothioate (PS) antisense oligonucleotides are currently used to inhi bit many cell functions both in vivo and in vitro. However, these modified oligos provide reasonable sequence specificity only within a narrow concent ration range. To overcome such a limitation we synthesized antisense oligom ers, partially phosphorothioated, targeted against the human N-myc mRNA. We utilized such modified oligomers in a human neuroblastoma cell line where the N-myc gene expression was very high, and compared them to full phosphor othioate oligonucleotides. Both full PS and partial PS antisense oligos pro duced a maximum reduction in target mRNA after 6 h of treatment. They were able to maintain a good level of inhibition for 20 h on ly at high concentr ation. While partial PS oligos produced a dose dependent and sequence speci fic inhibition of N-myc mRNA, full PS molecules suffer from some disadvanta ges at the highest concentration used. Our results showed that partial PS m olecules were capable of reducing gene expression showing a greater sequenc e specificity over a far broader concentration range. For this reason we co nclude that partial PS antisense oligos, with respect to full PS antisense oligos, might be particularly useful for studying gene function, J. Cell. B iochem. 74:31-37, 1999. (C) 1999 Wiley-Liss, Inc.