E. Tomlinson et Ap. Rolland, CONTROLLABLE GENE-THERAPY - PHARMACEUTICS OF NONVIRAL GENE DELIVERY SYSTEMS, Journal of controlled release, 39(2-3), 1996, pp. 357-372
Although most research on gene therapy has focused on the development
of viral-mediated approaches to deliver therapeutic genes to cells bot
h ex vivo and in vivo, non-viral gene medicines have emerged as a pote
ntially safe and effective gene therapy method for the treatment of a
wide variety of acquired and genetic diseases. Gene medicines consist
of bath a gene expression system that contains a therapeutic gene and
a synthetic gene delivery system. Gene expression systems can be const
ructed to control the location, amount and duration of in vivo product
ion of a therapeutic protein. A gene delivery system controls the dist
ribution and access of a gene expression system to a target tissue, it
s recognition by cell-surface receptors and its intracellular traffick
ing. As each biological target will require a unique gene delivery and
gene expression system, many of the principles and methods establishe
d in developing advanced drug delivery systems can be applied to the d
esign and preparation of synthetic gene delivery systems. This paper d
escribes different approaches taken to protect and to enhance the deli
very of gene expression systems to target cells. Self-assemblies of co
ndensing carriers, such as cationic liposomes, synthetic polymers and
peptides, with a gene expression system are described. The characteriz
ation of the resulting particulate gene medicines is reported, as is t
he influence of their physicochemical properties on the efficiency of
gene delivery. This contribution also describes approaches to effect t
he intracellular trafficking of a gene expression system to the nucleu
s of a target cell, in particular by using synthetic amphipathic pepti
des to control the endosomal release of plasmid DNA.