Immunoliposome-Mediated Delivery of Nucleic Acids: A Review of Our Laboratory's Experience

Abstract

Experiments performed in our laboratory or in collaboration with other groups demonstrating the delivery to cells of mono-, oligo- and polynucleotides from antibody-targeted small liposomes are reviewed. Biologically-active molecules delivered into cells via these liposomes include: phosphorylated derivatives of dideoxyuridine, which have activity against the human immunodeficiency virus; the oligonucleotide (2'-5') (A)_n and various analogues, which have anti-viral and antiproliferative activity; and antisense phosphodiester and phosphorothioate oligodeoxynucleotides, which may have both gene-specific and nonspecific effects. Polynucleotides include: the RNA duplex poly (rI:rC), and related molecules, which are inducers of interferon and other cytokines; long RNA antisense molecules and plasmids. Advantages for delivery by liposomes, as compared to use of the same molecules free in solution include: protection against degradation, reduction of toxicity, improved pharmacokinetics and the possibility of increased intracellular transport. Numerous parameters are important in determining if and to what extent liposome contents are delivered to their sites of action, including: liposome size, lipid composition, nature of the encapsulated molecule, type of ligand used for targeting and its linkage to the liposome, and the cell type and target molecule. The precise mechanism(s) whereby oligo- and polynucleotides are able to enter into the cytoplasm from endocytic vesicles, and the efficiency of this process are not well understood.