Phosphatase Inhibitor Cocktail

Several phosphate backbone variants have been developed in an attempt to alter the chemical properties of native-state DNA and therefore overcome the two major challenges involved with using oligonucleotides in vivo, including: 1) delivery to the interior of the cell through the plasma membrane, a lipid bilayer that without transport proteins, is mostly impermeable to polar molecules, and 2) extension of the effective molecular lifetime by minimizing extra and intracellular nuclease degradation.

One of the original and still most widely-used backbone variants is phosphorothioate (commonly referred to as S-oligo when incorporated into an oligonucleotide, Figure 1). Phosphorothioate has been found to help alleviate the second major challenge associated with using oligonucleotides in vivo by reducing the activity of a variety of extra and intracellular nucleases¹.