Control of scarring in adult wounds using antisense transforming growth factor‐β1 oligodeoxynucleotides

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Abstract
Adult wounds heal with scar formation, whereas fetal wounds heal without scarring and with a lesser inflammatory and cytokine response. We reasoned that a strategy employing antisense oligodeoxynucleotides (ODN) complementary to transforming growth factor (TGF)-1 mRNA might decrease the scarring of dermal wounds in the mouse. To evaluate this concept, we tested the effects of antisense ODN targeted to TGF-1 mRNA by topical application of the ODN on the skin wound. Phosphorothioation of ODN to retard their degradation. When antisense TGF-l ODN were applied on the wound site, there was a marked reduction of scarring compared with a control wound site. This effect of antisense TGF-1 ODN on scar formation was associated with decreased expression of the TGF-1 gene. However, sense TGF-pl ODN had no effect on the expression of the TGF-1 gene. In addition, control wounds healed with excessive fibrosis compared with the antisense-treated wounds. In conclusion, our results indicate that antisense TGF-1 ODN could be used for ameliorating scar formation during wound healing.