Gene delivery advantages

Although viral-mediated gene delivery systems currently predominate, a substantial number of current clinical trials use non-viral-based methods of gene delivery. General advantages quoted with respect to non-viral delivery systems include ... 

The gene delivery systems presented in this section represent those with the most information regarding characterization and application. Each system has advantages and disadvantages. For this reason, there may be a disease application for one type of system that is not suitable for another. A few years ago, gene therapy was criticized for the number of clinical trials that had been completed with little or no success. Only in the past few years have demonstrations of benefit been realized to validate the concept. The question is no longer will this form of therapy be employed to treat disease, but when it will be employed. 

The latter studies on pDNA delivery of a therapeutic gene to treat metabolic diseases, autoimmune diseases, viral infections or cancer suggest that naked pDNA could be used for gene delivery. The advantages of this type of therapy include the simplicity of i.m. injection, the requirement for only a limited number of i.m. injections to achieve measurable serum levels of the therapeutic protein, the maintenance of stable serum levels of the protein thereby avoiding side-effects associated with bolus protein delivery and the avoidance of the use of viral vectors which pose safety concerns and which can induce anti-vector antibodies. With improvements in pDNA design and delivery, this type of gene therapy may someday prove useful for therapy of a variety of human diseases. 

Chronologically, this is the second family of cationic lipids that were employed for gene delivery. The pioneering work was presented by Behr et al. (1989), who had proposed to take advantage of DNA condensing property of a naturally occurring polyamine, such as spermine. Indeed, during cell division,... 

The necessity of more efficient gene delivery methods prompted the search for novel, less charged or non-cationic gene delivery systems. These non-electrostatic complexes can be advantageous for in vitro and in vivo applications, since unlike cationic lipid/DNA complexes, the novel molecules could not lead to a compacted state of DNA, and could therefore potentially lead to different kinetics of DNA release from complexes. Several compounds are able to bind to double stranded DNA along the grooves by the formation... 

Ghosh YK, Visweswariah SS, Bhattacharya S (2002) Advantage of the ether linkage between the positive charge and the cholesteryl skeleton in cholesterol-based amphiphiles as vectors for gene delivery. Bioconjug Chem 13 378-384... 

Several amine functionalized hyperbranched PGs have been reported as potential gene delivery systems after a proper surface group functionalization. In comparison to other dendritic structures, these scaffolds have the added advantage of being open, flexible, and possessing a polyether backbone which keeps the toxicity profile low. Different systems have been studied by post-modification of the hydroxyl groups... 

Thiols are typically incorporated into polymers for gene delivery to take advantage of the reducing environment of the cytoplasm. Thiols can be mildly oxidized to produce disulfide (S-S) bonds for delivery vehicle crosslinking,... 

Polymer. The field of nonviral gene delivery using cationic polymers is at its early stage compared to that of cationic lipid. However, this system is also known to have advantages over lipid-based systems in controlling the size, charge, and other physicochemical properties. Polycation-DNA complexes, also called as polyplexes, are formed by a cooperative... 

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