Localized, direct plasmid gene delivery in vivo: prolonged therapy resultsin reproducible tissue regeneration

The inability to deliver growth factors locally in a transient but sustaine d manner is a substantial barrier to tissue regeneration. Systems capable o f localized plasmid gene delivery for prolonged times may offer lower toxic ity and should be well-suited for growth factor therapeutics. We investigat ed the potency of plasmid gene delivery from genes physically entrapped in a polymer matrix (gene activated matrix) using bone regeneration as the end point in vivo. implantation of gene activated matrices at sites of bone inj ury was associated with retention and expression of plasmid DNA for at leas t 6 weeks, and with the induction of centimeters of normal new bone in a st able, reproducible, dose- and time-dependent manner.