Liposome-based gene transfer

Liposomes Liposome-based gene transfer is anonviral gene delivery method that uses the combination of phospholipids, cholesterol, and some polymers for the formation of spherical vesicles. DNA is dehvered into cells by liposomes via membrane fusion and endocytosis. This method has several advantages such as enhanced delivery, nontoxicity, the protection of nucleic acids from nuclease activity, and the abihty to target DNA into a variety of ceU types, including protoplasts, via plasmodesmata. 

It was believed that the main factors affecting transfection efficiency were the structure of the cationic lipid, the type of helper lipid used and their susceptibility to disruption by serum proteins. For gene transfer in vivo, apart from DOTMA-based liposomes, other complexes (in equimolar ratios) are also used—such as dioctade-cylamidoglicylspermidin (DLS)/DOPE (137), DOPE/DOTMA (1 1), DOPE/DOTAP (1 1) (138, 139), dimethyloctadecylammonium bromide (DDAB), and DOTAP with cholesterol (1 1) (mol/mol) (139). 

Lipid/DNA particles represent a nonliposomal but lipid-based delivery system for gene transfer. Monomeric or micellar lipids are allowed to interact with DNA in the presence of detergent or some other surface-active agent that is then removed by dialysis. As the surface-active agent diffuses out, solid, condensed particles of lipid and DNA form (17). These can be prepared such that they are smaller and more homogeneous than liposome/DNA complexes yet transfect cells equally well (F. Wong, unpublished observations). 

Catheter-based, plasmid with Human iNOS fusigenic liposome Gene transfer for rapid re-endothelialization Phase I, human coronary artery REGENT-I... 

Nonviral gene transfer systems are based on a variety of technologies that employ physical/chemical means to deliver genes [6], These technologies include direct plasmid injection, bombardment with DNA coated microprojectiles, and DNA complexed with liposomes or polymers. Some nonviral transfection techniques are too inefficient (e.g., coprecipitation of DNA with calcium phosphate [7], DNA complexed with diethylaminoethyl (DEAE)-dextran [8], electroporation [9]), or laborious (e.g., microinjection of DNA [ 10 ]) for clinical use. Only those gene delivery systems (viral and nonviral) with potential for clinical application are discussed in this chapter. The main features of these technologies (Table 18.3) are described and specific examples of their applications highlighted. 

Liposomes have been investigated in the delivery of the gene-based drugs for more than a decade. The cellular transfer of genes and oligonucleotides is obtained with cationic lipo-... 

Protamine-based nanoparticles show a very low cytotoxicity in comparison with other gene delivery systems. In addition, when compared with commercially available liposomes (DOTAP, lipofectin), one artificial virus capsoid (polyoma VPl) and two cationic acrylate nanoparticles, the cell transfer efficiency in a mouse fibroblast cell line with protamine nanoparticles was one of the highest [117]. 

---