Gene Therapy in Bone Regeneration: A Summary of Delivery Approaches for Effective Therapies - Intracellular Delivery: Fundamentals and Applications - page 820

Fig. 2 (continued)
be partly responsible for this by clearing plasmid particles prematurely. Extended
gene expression is required to attain a biological response, so the plasmid DNA
complexes must be taken up by the cells over a sustained period of time. This
means the complexes must retain their stability in a high serum environment, in
addition to avoiding clearance by the immune system. A scaffold is beneficial to
prolong the presence of plasmid/carrier complexes and additionally provides an
attachment site for incoming cells and extracellular matrix production (De LaPorte
and Shea 2007 ). Although in vivo transfection is possible with naked DNA, a large
and economically-unsustainable amount of plasmid DNA is required in the absence
of a carrier. The latter is involved in compacting DNA molecules into a suitable size
for cellular uptake, lowering the dose required for effective cellular modification.
Gene carriers can also help protect the unmethylated plasmid DNA from premature
clearance by the immune system (Krieg 2002 ).