The use of synthetic polymers for delivery of therapeutic antisense oligodeoxynucleotides

Developed over the past two decades, the antisense strategy has become a te chnology of recognised therapeutic potential, and many of the problems rais ed earlier in its application have been solved to varying extents. However, the adequate delivery of antisense oligodeoxynucleotides to individual cel ls remains an important and inordinately difficult challenge. Synthetic pol ymers appeared on this scene in the middle 1980s, and there is a surprising ly large variety used or proposed so far as agents for delivery of oligodeo xynucleotides. After discussing the principles of antisense strategy, certa in aspects of the ingestion of macromolecules by cells, and the present Sit uation of delivery procedures, this article analyses in detail the attempts to use synthetic polymers as carrier matrices and/or cell membrane permeab ilisation agents for delivery of antisense oligodeoxynucleotides. Structura l aspects of various polymers, as well as the results, promises and limitat ions of their use are critically evaluated. (C) 2001 Elsevier Science Ltd. All rights reserved.