Nature Medicine
5, 753 - 759 (1999)
doi:10.1038/10473
Localized, direct plasmid gene delivery in vivo: prolonged therapy
results in reproducible tissue regenerationJeffrey Bonadio1, 3, Elizabeth Smiley1, Pravin Patil2
& Steven Goldstein21
Department of Pathology, University of Michigan Medical
School, Ann Arbor, Michigan 48109-0417,
USA
2
Orthopaedic Research Laboratories, University of Michigan Medical School, Ann Arbor, Michigan 48109-0486, USA
3
J.B. present address: Selective Genetics, 11035 Roselle Street, San Diego, California 92121, USA
Correspondence should be addressed to Jeffrey Bonadio jbonadio@selectivegenetics.comThe inability to deliver growth factors locally in a transient but sustained
manner is a substantial barrier to tissue regeneration. Systems capable of
localized plasmid gene delivery for prolonged times may offer lower toxicity
and should be well-suited for growth factor therapeutics. We investigated
the potency of plasmid gene delivery from genes physically entrapped in a
polymer matrix (gene activated matrix) using bone regeneration as the endpoint
in vivo. Implantation of gene activated matrices at sites of bone injury was
associated with retention and expression of plasmid DNA for at least 6 weeks, and with the induction of centimeters of normal new bone in a stable, reproducible, dose- and time-dependent manner.
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