Design, Biological Properties and Delivery of Antisense Oligonucleotides

Abstract

Antisense is the term used to describe the application of a nucleic acid of complementary sequence to the sense sequence of a messenger RNA, in order to downregulate gene expression by intervening in translation (Fig. 1). The antisense molecule can itself be an mRNA, and this has been found to occur as a natural regulatory mechanism (Murray, 1992). Or with more relevance to therapeutic approaches, the antisense molecule can be an oligonucleotide, that is synthesized chemically. Because it is easier to synthesize oligodeoxynucleotides than oligoribonucleotides using an automated procedure, these are the derivates that are used for most antisense applications. Since the area of antisense has been widely reviewed (Ghosh and Cohen, 1992; Murray, 1992), this article will contain only a brief introduction to the topic, and will then focus on the delivery of oligonucleotides as antisense compounds.