ABSTRACT
Since the late 1970s, antisense oligonucleotides have been used for the specifi c inhibition of gene expression (Stephenson and Zamecnik 1978). Upon hybridizing to their target ribonucleic acid (RNA), they sterically inhibit messenger ribonucleic acid (mRNA) translation or the correct splicing of precursor RNAs, and/or mediate RNA degradation through the action of ribonuclease H. The idea of the specifi c knockdown of the expression of a given target gene was also explored after the discovery of ribozymes in the early 1980s: catalytically active RNAs that sequence-specifi cally bind to and cleave their target mRNA. Both approaches, including deoxyribonucleic acid (DNA)- based ribozymes, have been studied quite extensively with regard to the development of nucleic acid molecules with optimal chemical modifi cations, and strategies for their delivery in vitro and in vivo.
