Isis pharmaceuticals: what is the sense in antisense?

Isis Pharmaceuticals have an impressive patent portfolio built upon their ability to synthesise modified synthetic oligonucleotides in large amounts. The use of these compounds to inhibit gene expression by blocking translation or activating RNase H has been demonstrated in vitro and one product is in Phase III clinical trials. Much depends upon the Company's ability to use antisense oligonucleotides designed to inhibit ras, raf, ICAM-1 and protein kinase C in disease tissues where these proteins are valid drug targets. Having established this, the question of drug delivery in whole animals will need to be addressed.