Antisense inhibition of phosphodiesterase expression.

Cyclic nucleotide phosphodiesterases (PDEs) are represented by a superfamily of structurally and functionally related enzymes of which more than 30 different forms have so far been identified and grouped into seven broad gene families, some of which contain multiple genes and many splice variants, within a given gene family. Since all of the forms of PDE have the potential to regulate levels of the second messenger, cAMP or cGMP, and some of the forms appear to be tissue specific in their expression and differentially regulated, it would be useful to be able to selectively inhibit a given form of PDE, to study the physiological consequences of this inhibition, with the intent of possible therapeutic application. While gene family-specific pharmacological inhibitors exist for six of the seven gene families, none of these inhibitors is yet capable of distinguishing PDE members within a given gene family in its inhibition. One approach to selectively inhibit a specific form of PDE, without affecting others, is through use of antisense oligonucleotides to block the expression of a given PDE form. This article describes ways to optimally develop and test antisense oligonucleotides to inhibit expression of PDE.