Delivery systems for antisense oligonucleotides

In vitro, the efficacy of the antisense approach is strongly increased by systems delivering oligodeoxyribonucleotides (ODNs) to cells. Up to now, most of the developed vectors favor ODN entrance by a mechanism based on endocytosis. Such is the case for particulate systems, including liposomes (cationic or non-cationic), cationic polyelectrolytes, and delivery systems targeted to specific receptors. Under these conditions, endosomal compartments may represent a dead end for ODNs. Current research attempts to develop conditions for escaping from these compartments. A new class of vectors acts by passive permeabilization of the plasma membrane. It includes peptides, streptolysin O, and cationic derivatives of polyene antibiotics. In vivo, the interest of a delivery system, up to now, has appeared limited. Development of vectors insensitive to the presence of serum seems to be a prerequisite for future improvements.