Liposomes as a carrier for intracellular delivery of antisense oligonucleotides: A real or magic bullet?

Antisense oligonucleotides are specific inhibitors of gene expression. They represent a promising tool in fighting viral, malignant and inflammatory diseases. In many cases their activity is limited by their low cellular uptake and lack of target cell recognition. One approach to circumvent these problems is the use liposomes as an oligonucleotide carrier. The encapsulation of oligonucleotides in liposomes is useful for several reasons: (1) protection of oligonucleotides from nuclease degradation; (2) enhancement of cellular uptake in several cell types; (3) improvement of oligonucleotide potency, especially in vitro; (4) modification of their intracellular distribution (this is particularly true for cationic liposomes); (5) increased retention of the oligonucleotides in cells; (6) potential for slow release depots for modified oligonucleotides. However, encapsulation of oligonucleotides in liposomes may decrease the access of the oligonucleotide to tissues outside of the vascular system which may restrict the use of oligonucleotides encapsulated in liposomes or other particulate carriers to accessible cells or tissues. In this review results obtained in vitro and in vivo, using liposome encapsulated oligonucleotides are described and the benefits of liposomes as an oligonucleotide carrier are analyzed.