The first goal of this review is to describe a local plasmid gene transfer
technology known as the gene activated matrix (GAM). GAM was the first gene
therapy designed specifically for tissue engineering applications, and the
mechanism of action of plasmid gene transfer is closely tied to the normal
sequence of events associated with wound healing. The normal sequence of w
ound healing events is stereotyped for most tissues, and one assumption has
been that GAM could serve as a platform technology for local gene delivery
in various tissues and organs. This hypothesis essentially has been proved
: animal studies over the past 6 years have established that plasmid genes
can be delivered to acutely injured tendon, ligament, bone, muscle, skin, a
nd nerve. The second goal of the review is to describe the most likely "fir
st use" of the technology in man, namely, treatment of osteoporotic hip fra
cture in the elderly. Although not universally appreciated, interest in ost
eoporotic fracture should grow because of epidemiological, surgical, and so
cietal considerations. These considerations, plus the unmet clinical need a
ssociated with the current standard of fracture care, justify efforts to de
velop novel therapies for bone regeneration and repair in the elderly.