INHIBITION OF TROPONIN-C PRODUCTION WITHOUT AFFECTING OTHER MUSCLE PROTEIN-SYNTHESIS BY THE ANTISENSE OLIGODEOXYNUCLEOTIDE

The effect of blocking expression of a specific gene with antisense ph osphodiester oligodeoxynucleotides on the coordinate regulation of myo genesis was studied. Different regions of both fast and slow troponin C (TnC) mRNAs were targeted for binding of the antisense oligomer. The 5'-cap region of both mRNAs was found to be the most effective target for inhibiting the expression of these genes. Approximately 40%-60% i nhibition of expression of a specific isoform of TnC was achieved. How ever, inhibition of the TnC expression did not appreciably alter the p attern of myogenesis of mouse C2C12 cells. The differentiated murine m uscle cells were able to cope with this reduced level of the target ge ne expression by antisense phosphodiester oligomers. We have also used a phosphorothioate oligomer targeted against a common sequence within the coding region of both fast and slow TnC mRNAs. This oligomer was found to be ineffective in blocking TnC gene expression.