ABSTRACT
Increased collagen expression during wound healing causes scar formation, abnormal contracture, low tensile strength, functional impairment, and disfigurement. A novel ex vivo wound-injury model demonstrated that AS60, an antisense oligonucleotide (ASO) to type I collagen, reduced the mRNA and protein expression of type 1 collagen. Following a cutaneous wound injury in a human-skin organ culture, AS60 injection resulted in a 36% (P < 0.001) and 30% decrease (P < 0.001) in type 1 collagen mRNA and protein expression after 7 days. Similarly, transfection of cultured human fibroblasts with ASO resulted in a 36% decrease (P < 0.001) and a 31% decrease (P < 0.001) in type 1 collagen mRNA and protein expression. Immunofluorescence of human skin organ culture treated with ASO showed a specific reduction in collagen expression. Using AS60 to reduce collagen expression in human skin may have implications for its use as a gene therapy agent to reduce the formation of fibrotic scarring.
