Localized, direct plasmid gene delivery in vivo: prolonged therapy results in reproducible tissue regeneration.
The 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.
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0417, USA. jbonadio@selectivegenetics.com
J
J
Bonadio
E
E
Smiley
P
P
Patil
S
S
Goldstein
D000818:Animals; D001861:Bone Regeneration; D004285:Dogs; D005269:Femur / Q000000981:diagnostic imaging / Q000293:injuries* / Q000473:pathology; D015316:Genetic Therapy; D006801:Humans; D010027:Osteotomy; D010281:Parathyroid Hormone / Q000235:genetics*; D010957:Plasmids; D011859:Radiography; D011994:Recombinant Proteins / Q000378:metabolism; D019379:Teriparatide / Q000008:administration & dosage / Q000627:therapeutic use*; D013977:Tibia / Q000000981:diagnostic imaging / Q000293:injuries* / Q000473:pathology
D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D019379:Teriparatide