Liposome-Mediated Gene Delivery: Dependence on Lipid Structure, Glycolipid-Mediated Targeting, and Immunological Properties

Abstract

This chapter outlines the methodological aspects of gene delivery by a novel set of lipidic transfection reagents, including cationic lipids, glycolipids, and pH-sensitive and neutral lipids. Various methods used in gene transfer, and new methods for the estimation of the influence of these compounds on the complement systems are described along with both in vitro and in vivo gene delivery methods. Lipids include the pH-sensitive/neutral structures I and II; the cationic lipids III, IV, V, and VI; the oligocationic molecules VII, VIII, and IX; the dicationic XII; the glycocationic molecule XI; and the glycolipid X in vitro and in vivo.. The chapter presents a series of novel lipids with a range of transfection activities. The choice of lipids and DNA/lipid ratios depends on the actual application of the gene transfer technology to a particular therapy. Lipoplexes that mediate high levels of transgene activity in one tissue may not be desirable for gene delivery in another tissue. It should also be considered that achieving high transfection activity may be associated with high toxicity on the complement system. Thus, the choice of a non-viral vector for gene delivery in vivo depends on weighing its advantages and limitations in a particular application.