Oligonucleotides can be used to control gene expression according to several strategies. In the antisense approach the oligonucleotide is targeted to a messenger RNA, thereby inhibiting translation, or to a viral RNA (or single-stranded DNA) where it can control RNA or DNA replication or reverse transcription. An oligodeoxynucleotide is able to induce cleavage of the target RNA via activation of an endogenous RNase H. An oligoribonucleotide may also induce catalytic cleavage of RNA in the absence of any protein (ribozyme). Antisense RNAs and ribozymes can be synthesized within cells via genetic constructs. In the sense approach the oligonucleotide is used to bind a protein: a single-stranded oligoribonucleotide can be used to trap viral proteins, such as tat and rev from HIV; a double-stranded oligonucleotide can act as a trap for a transactivating factor involved in the control of transcription. In the antigene strategy the oligonucleotide binds to a specific sequence of DNA, thereby forming a triple helix that may inhibit transcription of the target gene. This review presents the latest developments of this new strategy to control gene expression. Reviews of the other strategies are presented elsewhere.'. 2