Synthetic peptide-based DNA complexes for nonviral gene delivery

Abstract

A major advantage of synthetic peptide-based DNA delivery systems is its flexibility. By design, the composition of the final complex can be easily modified in response to experimental results in vitro and in vivo to take advantage of specific peptide sequences to overcome extra- and intracellular barriers to gene delivery. The extreme heterogeneity which greatly complicates both the kinetics of DNA–poly( l-lysine) interaction and the thermodynamic stability of the final DNA complexes is avoided. Other unique features include the absence of biohazards related to the viral genome as well as the production of the viral vector and the absence of limitations on the size of the therapeutic genes that can be inserted in the recombinant viral vector. In principle, if the gene can be cloned into an expression plasmid, it can be delivered as a synthetic DNA complex. Since these synthetic delivery systems are composed of small peptides which may be poorly antigenic, they hold the promise of repeated gene administration, a highly desirable feature which will be important for gene targeting in vivo to endothelial cells, monocytes, hepatocytes and tumor cells.