Cationic liposomes as non‐viral carriers of gene medicines: Resolved issues, open questions, and future promises

Abstract

The clinical success of gene therapy is critically dependent on the development of efficient and safe gene delivery reagents, popularly known as "transfection vectors." The transfection vectors commonly used in gene therapy are mainly of two types: viral and non-viral. The efficiencies of viral transfection vectors are, in general, superior to their non-viral counterparts. However, the myriads of potentially adverse immunogenic aftermaths associated with the use of viral vectors are increasingly making the non-viral gene delivery reagents as the vectors of choice. Among the existing arsenal of non-viral gene delivery reagents, the distinct advantages associated with the use of cationic transfection lipids include their: (a) robust manufacture; (b) ease in handling and preparation techniques; (c) ability to inject large lipid:DNA complexes; and (d) low immunogenic response. The present review highlights the major achievements in the area of designing efficacious cationic transfection lipids, some of the more recent advances in the field of cationic liposomes-mediated gene transfer and targeted gene delivery, some unresolved issues and challenges in liposomal gene delivery, and future promises of cationic liposomes as gene-carriers in non-viral gene therapy.

Dendritic Polyglycerols for Biomedical Applications

“…Cationic lipids and cationic polymers are the best studied compounds for this purpose. [214,215] The interaction between a single protonated amine and the phosphate backbone of DNA is relatively weak and competes with salt binding under biological conditions. Therefore tetra-amines such as spermine are used to achieve DNA binding.…”

Electrolyte Solution at Zwitterionic Lipid Layer

“…[1][2][3] The pure cationic lipids in bilayer interact with negatively charged DNA electrostatically and form polyplexes 4 . The major weaknesses of using cationic lipids are the relatively low transfection efficiency and cytotoxicity.…”

Synergistic effects on gene delivery – co-formulation of small disulfide-linked dendritic polycations with Lipofectamine 2000™

“…3 Two classes of vector have seen particularly intensive development -cationic polymers 4 and cationic lipids. 5 Cationic polymers achieve DNA binding and delivery owing to their large number of cationic sites which can effectively bind polyanionic nucleic acid -however, polycations are known to be toxic in vivo, leading to hemolysis and other unwanted side effects. Cationic lipids, on the other hand, bind DNA as they assemble multiple positively charged units in a non-covalent manner.…”