Antisense therapeutics: from theory to clinical practice

The use of amisense (AS) oligonucleotides as therapeutic agents was proposed as far back as the 1960s/1970s when the AS strategy was initially developed. However, it has taken almost a quarter of a century for this potential to be realized. The last few years has seen a rapid increase in the number of AS molecules progressing past Phase I in clinical trials, due in part to our increased knowledge of their structure and chemistry. Here, we describe the most prominent of these modifications with respect to clinical applicability. However, the main focus of this review is clinical application, with a, focus on cancer. We will discuss in detail both the status of the current AS clinical trials and the molecules that are likely to be the targets of the next group of AS molecules entering the clinic. (C) 2003 Elsevier Science Inc. All rights reserved.