Neoglycoconjugates for the delivery of nucleic acids into eucaryotic cells

Abstract

А development of stable and safety non-viral transport systems for delivery of therapeutic nucleic acids (NA) into the target cells is one of the problem of gene therapy. Cationic liposomes are promising delivery systems capable to transfer various kind of NA. However, the wide application of cationic liposomes for gene therapy purposes is limited by their low efficiency and unspecific NA delivery into cells. These drawbacks are related to the presence of different biological barriers for lipoplexes: the instability in biological fluids, the interaction with blood serum proteins, plasmatic and nucleic membranes and endosomal degradation. Modular gene delivery systems introduced ten years ago consist of different lipophilic modules that mediate environmental and cellular receptors interactions as well as intracellular trafficking. Modular systems containing synthetic neoglycolipids are widely used for development of targeted gene delivery based on specific carbohydrate-lectin interactions (glycotargeting). This review combines examples of neoglycolipids used as active components of cationic liposomes. Targeted delivery of plasmid DNA, mRNA, oligonucleotides and small interfering RNA into hepatocytes, Kupffer cells and dendritic cells are discussed.

Keywords

• liposomes, neoglycoconjugates, nucleic acids, targeted delivery, gene therapy.