Cell Biological and Biophysical Aspects of Lipid-mediated Gene Delivery

Abstract

Cationic lipids are conceptually and methodologically simple tools to deliver nucleic acids into the cells. Strategies based on cationic lipids are viable alternatives to viral vectors and are becoming increasingly popular owing to their minimal toxicity. The first-generation cationic lipids were built around the quaternary nitrogen primarily for binding and condensing DNA. A large number of lipids with variations in the hydrophobic and hydrophilic region were generated with excellent transfection efficiencies in vitro. These cationic lipids had reduced efficiencies when tested for gene delivery in vivo. Efforts in the last decade delineated the cell biological basis of the cationic lipid gene delivery to a significant detail. The application of techniques such as small angle X-ray spectroscopy (SAXS) and fluorescence microscopy, helped in linking the physical properties of lipid:DNA complex (lipoplex) with its intracellular fate. This biological knowledge has been incorporated in the design of the second-generation cationic lipids. Lipid-peptide conjugates (peptoids) are effective strategies to overcome the various cellular barriers along with the lipoplex formulations methodologies. In this context, cationic lipid-mediated gene delivery is considerably benefited by the methodologies of liposome-mediated drug delivery. Lipid mediated gene delivery has an intrinsic advantage of being a biomimetic platform on which considerable variations could be built to develop efficient in vivo gene delivery protocols.

Induction of genuine autophagy by cationic lipids in mammalian cells

“…8 Positively charged cationic liposomes interact electrostatically with negatively charged nucleic acid sequences to form complexes, which enter a cell through endocytosis. 31 It was well accepted that lipids were important components of autophagosomes.…”

“…3 Compared to viral vectors, nonviral delivery has the advantages of relatively high safety and ease of use. 4,5 A variety of nonviral vectors, including those based on calcium phosphate, 6 cationic lipids, 7,8 peptides 9 and polymers, 10 have been developed over the years. Among them, cationic lipids represent one of the most widely used classes of vectors, and many transfection products based on cationic lipids are commercially available.…”

Chapter 10 Infrared and Raman Microscopy in Cell Biology

“…These are bilayer-based nanospheres with sizes ranging from ∼50 to 300 nm. Currently, liposomes are widely used for drug delivery purposes (Gupta et al, 2005), including intracellular drug and gene delivery (Rao and Gopal, 2006;Serpe et al, 2006). Many aspects related to the detailed mechanisms of the liposome-to-cell interaction remain unresolved.…”

Arginine-based cationic liposomes for efficient in vitro plasmid DNA delivery with low cytotoxicity

“…39 The physicochemical properties (ie, size and zeta potential) of lipoplexes strongly influence their gene delivery efficiency. [40][41][42] It has been reported that lipoplexes with larger particle size show elevated transfection efficiency because of their maximum contact with the cells, and larger particles taken up by cells lead to the formation of large intracellular vesicles that are more easily disrupted, thus releasing DNA into the cytoplasm. 43 Our data also indicate that larger lipoplex particles formed when prepared in the absence of serum than when in the presence of serum and thus elevated transfection efficiency in the absence of serum.…”