Liposomes for DNA/RNA Delivery

Liposomes are vesicular structures, and the unique advantages imparted by lipid vesicles are their diverse range of morphologies, compositions, abilities to envelope and protect many types of therapeutic biomolecules, lack of immunogenic response, low cost, and their differential release characteristics. These characteristics have led to applications in chemical and biochemical analytics, cosmetics, food technologies, and drug and gene delivery. There are numerous lipid formulations for each of these applications. This article is mainly about the use of liposomes for gene delivery.

1. Which Type of Liposomes Are Used for Gene Delivery?

Liposomes are generally formed by the self-assembly of dissolved lipid molecules, each of which contains a hydrophilic head group and hydrophobic tails. Lipid molecules used in liposomes are conserved entities with a head group and hydrophobic hydrocarbon tails connected via a backbone linker such as glycerol. Cationic lipids commonly attain a positive charge through one or more amines present in the polar head group. The presence of positively charged amines facilitates binding with anions such as those found in DNA. The liposome thus formed is a result of energetic contributions by Van der Waals forces and electrostatic binding to the DNA which partially dictates liposome shapes. Because of the polyanionic nature of DNA, cationic (and neutral) lipids are typically used for gene delivery, while the use of anionic liposomes has been fairly restricted to the delivery of other therapeutic macromolecules.

1. Why Is Liposome Mediated Gene Delivery Preferred?

When compared to viral-based carriers, liposomal gene delivery systems offer several advantages, including the absence of viral components, the protection of the DNA/RNA from inactivation or degradation, and the possibility for cell-specific targeting.

2. How Does Liposome Deliver Genetic Material?

Lipid delivery systems are generated by a combination of plasmid DNA and a lipid solution that result in the formation of a liposome. This fuses with the cell membranes of a variety of cell types, introducing the plasmid DNA into the cytoplasm and nucleus, where it is transiently expressed. Existing research has found that many carcinoma cells, including oral squamous cancer cells, express high levels of folate receptor. Linkage of DNA or DNA-lipid complexes to folate can specifically target cancer cells. Pre-clinical studies have demonstrated the potential utility of linking targeting moieties to the gene therapy construct. The DNA can then be internalized via receptor-mediated endocytosis.

3. How Do liposomes Attach to DNA?

Upon interacting with negatively charged DNA, cationic liposomes form clusters of aggregated vesicles. At a critical density the DNA is condensed and becomes encapsulated within a lipid bilayer, although it is possible that the liposomes bind along the surface of the DNA, retaining its shape.

References

1. Balazs, et al.; Liposomes for use in gene delivery.Journal of drug delivery.
2. Sternberg, et al.;Ultrastructural Morphology Of Cationic Liposome/DNA Complexes For Gene Therapy: Correlation To Transfection Activity. Microscopy and Microanalysis. 1999, S2: 1108-1109.
3. Mali, Shrikant. Delivery systems for gene therapy. Indian journal of human genetics. 2013, 1: 3.