text: Antisense oligonucleotides were discovered in 1978 by Paul Zamecnik and Mary Stephenson. Oligonucleotides, which are short nucleic acid fragments, bind to complementary target mRNA molecules when added to the cell. These molecules can be composed of single-stranded DNA or RNA and are generally 13–25 nucleotides long. The antisense oligonucleotides can affect gene expression in two ways: by using an RNase H-dependent mechanism or by using a steric blocking mechanism.  RNase H-dependent oligonucleotides cause the target mRNA molecules to be degraded, while steric-blocker oligonucleotides prevent translation of the mRNA molecule. The majority of antisense drugs function through the RNase H-dependent mechanism, in which RNase H hydrolyzes the RNA strand of the DNA/RNA heteroduplex. expression.