The first antisense experiments used unmodified oligos, but they found that the cellular nucleases degraded the oligos quickly, leaving only a short time for the oligo to find its target. Oligos containing phosphorothioated bonds are more resistant to nuclease degradation. There are two options for inserting phosphorothioate bonds into an antisense oligo: either modifying the entire backbone or just capping the ends by putting three thioate bonds on each end of the oligo. Thioate bonds lower the Tm of your oligo, and the more thioate bonds you have, the greater the affect on the final Tm. Therefore, we usually recommend capping the oligo. We also strongly recommend HPLC purification and a Sodium Salt Exchange because the chemical byproducts of the synthesis/purification can be toxic to your cells.