Delivery systems for antisense oligonucleotides

In vitro, the efficacy of the antisense approach is strongly increased by s ystems delivering oligodeoxyribonucleotides (ODNs) to cells. Up to now, mos t of the developed vectors favor ODN entrance by a mechanism based on endoc ytosis. Such is the case for particulate systems, including liposomes (cati onic or non-cationic). cationic polyelectrolytes, and delivery systems targ eted to specific receptors. Under these conditions, endosomal compartments may represent a dead end for ODNs. Current research attempts to develop con ditions for escaping from these compartments. A new class of vectors acts b y passive permeabilization of the plasma membrane. It includes peptides, st reptolysin O, and cationic derivatives of polyene antibiotics. In vivo, the interest of a delivery system, up to now, has appeared limited. Developmen t of vectors insensitive to the presence of serum seems to be a prerequisit e for future improvements. (C) 2000 Elsevier Science Inc. All rights reserv ed.