Comparison and evaluation of gene therapy and epigenetic approaches for wound healing

During the past decade considerable evidence has mounted concerning the imp ortance of growth factors in the wound healing process both for cell replic ation and for stimulating reparative cells to synthesize and secrete extrac ellular matrix components. During normal wound healing the growth factor co ncentration has to be maintained at a certain level. If the growth factor c oncentration is too low, normal healing fails to occur. Whereas if the grow th factor concentration is too high due to either over-expression of the gr owth factor or too much growth factor being applied to the wound, aberrant wound healing will occur. One approach for controlling the amount of growth factor at the wound site during normal healing is through gene therapy and the titration of gene dosage. However if a narrow window exists between th e beneficial therapeutic effect and toxic effects with increasing gene dosa ge, an agent may be necessary to give in combination with gene therapy to r egulate the over-expression of growth factor. In addition to genetic approa ches to regulate wound healing, epigenetic approaches also exist. Antisense oligodeoxynucleotides have been shown to regulate wound repair in certain model systems and to determine the protein(s) necessary for normal wound he aling. A novel approach to regulate the activity of collagen genes, thereby affecting fibrosis, is to use a sense oligodeoxynucleotide having the same sequence of the cis element which regulates the promoter activity of a par ticular collagen gene. This exogenous oligodeoxynucleotide will compete wit h the cis element in the collagen gene for the trans-acting factor which re gulates promoter activity. These epigenetic approaches afford the opportuni ty to regulate over-expression of growth factor and therefore preclude the potential toxic effects of gene therapy. Both genetic and epigenetic approa ches for regulating the wound healing process, either normal or aberrant wo und healing, have certain advantages and disadvantages which are discussed in the present article.