Therapeutic Oligonucleotides

A brief historical introduction describes early attempts to silence specific genes using the antisense oligonucleotides that flourished in the 1980s. Early aspirations for therapeutic applications were almost extinguished by the unexpected complexity of oligonucleotide pharmacology. Once the biochemistry and molecular biology behind some of the pharmacology was worked out, new approaches became apparent for using oligonucleotides to treat disease. The biochemistry of small nucleic acids is outlined in Section 2. Various approaches employing oligonucleotides to control cellular functions are reviewed in Section 3. These include antisense oligonucleotides and siRNA that bind to RNA, antigene oligonucleotides that bind to DNA, and aptamers, decoys, and CpG oligonucleotides that bind to proteins.