Targeting Antisense Oligonucleotide Chemotherapy to the Type I Regulatory Subunit of cAMP-Dependent Protein Kinase

Abstract

Antisense RNA sequences have been described as naturally occurring biological inhibitors of gene expression in both prokaryotes (Mizuno et al., 1984) and eukaryotes (Heywood, 1986), and these sequences presumably function by hybridizing to complementary mRNA sequences, resulting in hybridization arrest of translation (Paterson et al., 1977). Antisense oligodeoxynucleotides are short synthetic nucleotide sequences formulated to be complementary to a specific gene or RNA message. Through the binding of these oligomers to a target DNA or mRNA sequence, transcription or translation of the gene can be selectively blocked, and the disease process generated by that gene can be halted. The cytoplasmic location of mRNA provides a target considered to be readily accessible to antisense oligodeoxynucleotides entering the cell; hence, much of the work in the field has focused on RNA as a target.