In vivo transfer and expression of a human epidermal growth factor gene accelerates wound repair.
This report details the transfer of a human epidermal growth factor (hEGF) expression plasmid to porcine partial-thickness wound keratinocytes by particle-mediated DNA transfer (Accell). After gene transfer an external sealed fluid-filled wound chamber was used to protect the wound, provide containment of the exogenous DNA and expressed peptide, and permit sampling of the wound fluid. Analysis of wound fluid for hEGF and total protein, an indicator of reformation of the epithelial barrier, showed that wounds bombarded with the hEGF plasmid exhibited a 190-fold increase in EGF concentration and healed 20% (2.1 days) earlier than the controls. EGF concentrations in wound fluid persisted over the entire 10-day monitored period, decreasing from 200 pg/ml to 25 pg/ml over the first 5 days. Polymerase chain reaction results showed that plasmid DNA was present in the wound for at least 30 days. These findings demonstrate the possible utility of in vivo gene transfer to enhance epidermal repair.
Andree
C
C
Division of Plastic Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Swain
W F
WF
Page
C P
CP
Macklin
M D
MD
Slama
J
J
Hatzis
D
D
Eriksson
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001681:Biological Assay; D002455:Cell Division; D004247:DNA / Q000032:analysis; D017931:DNA Primers; D004815:Epidermal Growth Factor / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology; D005091:Exons; D018014:Gene Transfer Techniques; D006801:Humans; D007624:KB Cells; D015603:Keratinocytes / Q000502:physiology*; D008969:Molecular Sequence Data; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013552:Swine; D013997:Time Factors; D014945:Wound Healing; D014947:Wounds and Injuries / Q000503:physiopathology* / Q000628:therapy
D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D004247:DNA