The development of vectors for cell-specific gene delivery is a major goal
of gene therapeutic strategies. Significant progress has been made in the c
onstruction of non-viral vectors that combine different functions required
for gene transfer in an artificial complex. To some extent this can be achi
eved by complexing plasmid DNA with synthetic compounds such as lipids and
polycations. Alternative approaches rely on the activities of natural or re
combinant DNA-carrier proteins to achieve uptake and intracellular delivery
of plasmid DNA. Nuclear proteins such as histones and members of the high
mobility group protein family have been shown to condense DNA and transfect
cultured cells. Some structural proteins of DNA viruses spontaneously asse
mble with plasmid DNA and form transfection-competent pseudocapsids. In add
ition, chimeric fusion proteins have been engineered that incorporate in a
single polypeptide chain heterologous protein domains which facilitate bind
ing to plasmid DNA, specific recognition of target cells, induction of rece
ptor-mediated endocytosis, and DNA transport through intracellular compartm
ents. (C) 2000 Elsevier Science B.V. All rights reserved.