Reduction of dermal scarring

Patent Number: 7,465,442

TGF-beta is a multi-functioning cytokine with activities in a variety of physiological processes, including suppression of inflammation, protecting the bone marrow from stress, and stimulation of fibrosis.  TGF-beta is known to inhibit cell cycle progression in part by turning on p21.sup.WAF1/Cip1 (p21), which is a cyclin dependent kinase inhibitor. 

This patent covers the gene delivery of p21 using replication deficient adenoviruses to prevent scarring after wounding.  In its broadest claim, the patent covers "A method for reducing scarring, the method comprising administering a replication deficient adenoviral vector comprising an expression cassette to a wound on the skin of a subject, wherein the expression cassette comprises a promoter operably linked to a polynucleotide encoding p21.sup.WAF1/Cip1 and wherein the p21.sup.WAF1/Cip1 is expressed, resulting in wound closure and reduced scarring."

The approach used is very interesting because the inventors took one subcomponent of one signalling pathway and selectively used it only for its therapeutic effect.  This approach would be similar to taking TNF, which turns on numerous pathways, and selectively activating only the ones associated with tumor killing but not the anti-apoptotic activities that also are turn on by TNF through upregulation of NF-kB.

In the future we will see more approaches similar to the current patent in which subpathways of a pathway are turned on in order to maximize the specific effect that was desired (eg here the healing effects of TGF-beta are observed but not the fibrotic effects since only p21 was turned on and not the SMADs and other proteins). 

View this patent on the USPTO website.