A major advantage of synthetic peptide-based DNA delivery systems is i
ts flexibility. By design, the composition of the final complex can be
easily modified in response to experimental results in vitro and in v
ivo to take advantage of specific peptide sequences to overcome extra-
and intracellular barriers to gene delivery. The extreme heterogeneit
y which greatly complicates both the kinetics of DNA-poly(L-lysine) in
teraction and the thermodynamic stability of the final DNA complexes i
s avoided. Other unique features include the absence of biohazards rel
ated 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 t
hat 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 ar
e composed of small peptides which may be poorly antigenic, they hold
the promise of repeated gene administration, a highly desirable featur
e which will be important for gene targeting in vivo to endothelial ce
lls, monocytes, hepatocytes and tumor cells. (C) 1998 Elsevier Science
B.V.