Gene Therapy in Bone Regeneration: A Summary of Delivery Approaches for Effective Therapies - Intracellular Delivery: Fundamentals and Applications - page 819

effective in immunocompotent animals (Kang et al. 2004 ; Li et al. 2003a, b ; Alden
et al. 1999 ), and require immuno-suppression for a therapeutic effect (Kaihara et al.
2004 ), making them difficult to translate to a clinical setting. The non-viral
approach aims to delivery carrier/DNA complexes locally, so that the patient cells
at the repair site become transfected and produce the growth factor (Fig. 2b ).
Biomaterial scaffolds provide an easy vehicle with which to deliver the complexes,
making the administration of the complexes facile to a repair site. Cells invade the
scaffold and become transfected after taking up the resident complexes. Growth
factor for which the plasmid codes is produced locally, facilitating bone regenera-
tion and healing. Although much effort has been devoted to non-viral gene delivery,
the majority of such systems have been tested in vitro only and in vitro perfor-
mances do not correlate well with in vivo studies (Wang et al. 1998 ) due to unreal-
istic choice of experimental conditions in vitro . The immune system is thought to
Fig. 2 ( a ) Ex-vivo modification of cells for grafting into a host. The patient's cells are harvested
from bone marrow aspirate (or other sites), expanded in culture, and then transfected with the
growth factor gene of interest. Cells that are positive for growth factor are selectively expanded or
purified from unmodified cells, and administered to the patient. ( b ) In vivo approach to gene
delivery. A scaffold is loaded with complexes containing plasmid DNA for a growth factor expres-
sion, and administered into a bone defect. The patient's cell invade the scaffold, internalize the
complexes and expresses the desired growth factor, facilitating healing and bone regeneration