DNA–Lipid Amphiphiles for Drug and Gene Therapy

Abstract

Gene therapy is defi ned as the introduction of exogenous genetic materials including both DNA and RNA into a target tissue with the aim of providing therapeutic benefi t. Gene therapy holds great promise in treating diseases ranging from inherited disorders, to cancer, to acquired conditions. The genetic material being introduced has encoded genetic sequence functions to replace defective genes. Gene expression occurs by synthesizing functional gene products using the newly introduced genetic material. The introduced genetic material can also function to substitute missing genes, silence unwanted gene expression, or introduce new cellular biofunctions. 1,2 Gene therapy is often hampered by the need to overcome both the extracellular and the intracellular barriers. Before the gene can reach the target cells, it is subject to removal from opsonins, phagocytes, and degradative enzymes. Once it has penetrated through extracellular matrices and reaches the target cells, it is often limited by poor penetration into the cell membrane, lack of recognition characteristics necessary for intracellular transport, degradation within lysosomal compartments, and inability to release from transport vesicles. An effi cient delivery carrier is therefore required to protect the genetic materials and facilitate cellular uptake. 2 Gene delivery carriers can be classifi ed as viral and nonviral. In this chapter, the use of viral and nonviral gene delivery carriers will be discussed, with a focus on nonviral cationic liposome gene carriers. This chapter will also discuss on cationic liposomes ’ therapeutic applications, their structural – functional relationship, preparation methods, characterization methods, toxicity effects, challenges in delivery, their cellular pathways, and performance evaluation.