Cationic liposome–nucleic acid complexes for gene delivery and gene silencing

Abstract

Cationic liposomes (CLs) are studied worldwide as carriers of DNA and short interfering RNA (siRNA) for gene delivery and gene silencing, and related clinical trials are ongoing. Optimization of transfection efficiency and silencing efficiency by cationic liposome carriers requires a comprehensive understanding of the structures of CL–nucleic acid complexes and the nature of their interactions with cell membranes as well as events leading to release of active nucleic acids within the cytoplasm. Synchrotron x-ray scattering has revealed that CL–nucleic acid complexes spontaneously assemble into distinct liquid crystalline phases including the lamellar, inverse hexagonal, hexagonal, and gyroid cubic phases, and fluorescence microscopy has revealed CL–DNA pathways and interactions with cells. The combining of custom synthesis with characterization techniques and gene expression and silencing assays has begun to unveil structure–function relations in vitro. As a recent example, this review will briefly describe experiments with surface-functionalized PEGylated CL–DNA nanoparticles. The functionalization, which is achieved through custom synthesis, is intended to address and overcome cell targeting and endosomal escape barriers to nucleic acid delivery faced by PEGylated nanoparticles designed for in vivo applications.

Patterned Threadlike Micelles and DNA-Tethered Nanoparticles: A Structural Study of PEGylated Cationic Liposome–DNA Assemblies

“…: related to the spontaneous curvature of the membrane), the membrane bending rigidity and Gaussian modulus. 4 Other parameters which influence phase behavior include PEG-lipid grafting density and ionic strength of the formation buffer. 50 In this work, we investigated the effect of DNA length and topology.…”

“…lamellar, inverse hexagonal and gyroid cubic phases) that depends on the elastic properties of the membrane (spontaneous curvature, bending modulus, Gaussian modulus) and in some cases nucleic acid length. 4,33–35 …”

Cationic liposome–nucleic acid nanoparticle assemblies with applications in gene delivery and gene silencing

“…cystic fibrosis) and complex multi-gene diseases such as cancer [1]. Cationic liposomes (CLs, closed spherical assemblies of lipids) are the most prevalent synthetic vector [2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Gene delivery using cationic lipid-based vectors, termed lipofection, suffers from low transfection efficiency (TE; the ability to transfer DNA into cells followed by expression) in vivo in comparison with engineered viral vectors but also has advantages.…”

Recent progress in gene therapy to deliver nucleic acids with multivalent cationic vectors

“…These were mainly directed to specific aspects of the compaction process, as the molecular characteristics of the hydrophobic regions and/or headgroups, and of the lipoplex structure [11,15,[20][21][22][23][24][25], the biochemical behavior [26][27][28][29][30], the structure-biological activity relationship [9,21,[31][32][33][34][35], or to several of them [7,8,10,13,36,37]. On the other hand, several reviews have been centered in polyplexes [14,[38][39][40][41] or in a wide variety of nanocarriers [16,17,[42][43][44].…”