Antisense oligonucleotides: basic concepts and mechanisms.

Conceptual simplicity, the possibility of rational design, rel-atively inexpensive cost, and developments in the sequenc-ing of human genome have led to the use of short fragments of nucleic acid, commonly called oligonucleotides, either as therapeutic agents or as tools to study gene function. Fur-thermore, in the past decade, the development of antisense oligonucleotide technologies as therapeutics agents has led to Food and Drug Administration approval for the commer-cialization of the first antisense oligonucleotide, Vitravene (for cytomegalovirus retinitis; Refs. 1 and 2), and to numerous clinical trials of therapeutic oligonucleotides (3). The concept underlying antisense technology is relatively…