Use of nucleic acids with reduced pressure therapy

Abstract

Provided is a method of treating a wound site. Also provided is a system for treating a wound site. Additionally provided is the use of reduced pressure and a nucleic acid that promotes wound healing for treatment of a wound site. Further provided is the use of a nucleic acid that promotes wound healing for the manufacture of a medicament for treating a wound site that is undergoing reduced pressure treatment.

We claim: 
     
         1 . A method of treating a wound site, the method comprising
 applying a nucleic acid that promotes wound healing to the wound site, and   applying a reduced pressure to the wound site.   
     
     
         2 . The method of  claim 1 , wherein the wound site comprises dermal tissue, bone tissue, cartilage, tendon, ligament, nerve tissue, or adipose tissue. 
     
     
         3 . The method of  claim 1 , wherein the nucleic acid encodes a protein. 
     
     
         4 . The method of  claim 3 , wherein the nucleic acid is operably linked to a control element that directs expression of the protein when the nucleic acid is inside a cell in the wound site. 
     
     
         5 . The method of  claim 3 , wherein the protein is a structural protein, an enzyme, an enzyme inhibitor, a cell surface receptor or a transcription factor. 
     
     
         6 . The method of  claim 5 , wherein the protein is a collagen, a fibronectin, an elastin, a laminin, a Tie-1, a Tie-2, a c-kit, an HIF-1α, a tissue inhibitor of metalloproteinase, an integrin, a HoxD3, an hypoxia-inducible factor-1α (HIF-1α), or a Net. 
     
     
         7 . The method of  claim 3 , wherein the protein is a cytokine. 
     
     
         8 . The method of  claim 7 , wherein the cytokine is a fibroblast growth factor (FGF), a vascular endothelial growth factor (VEGF), a platelet derived growth factor (PDGF), a transforming growth factor-β (TGFβ), a TGFα, a stem cell factor (SCF), an angiopoietin 1 (Ang1), an epidermal growth factor (EGF), an interleukin, an insulin-like growth factor (IGF), a laminin, a hepatocyte growth factor (HGF), an adrenomedullin, a keratinocyte growth factor (KGF), a bone morphogenic protein (BMP), a cartilage derived morphogenic protein (CDMP), or a placental growth factor (PIGF). 
     
     
         9 . The method of  claim 3 , wherein the nucleic acid encodes a protein that increases expression in response to reduced pressure treatment of the wound site. 
     
     
         10 . The method of  claim 9 , wherein the protein is interleukin 6 (IL-6), chemokine ligand 7 (Ccl7), tissue inhibitor of metalloproteinase 1 (TIMP1), integrin alpha M (Itgam), suppressor of cytokine signaling 3 (Socs3), matrix metalloproteinase-8 (MMP-8), macrophage inflammatory protein-1 alpha receptor (MIP1), toll like receptor 1 (TLR1), tumor necrosis factor receptor superfamily member 1b (Tnfrsf1b), heat shock protein 70 (Hsp70), calmodulin-like 3, or keratin complex 1 acidic 14 (Krt1-14). 
     
     
         11 . The method of  claim 1 , wherein the nucleic acid specifically inhibits expression of a protein that inhibits wound healing. 
     
     
         12 . The method of  claim 11 , wherein the protein that inhibits wound healing is a small mothers against decapentaplegic homolog 3 (Smad3), a vascular endothelial growth factor receptor 1 (VEGFR1), a VEGFR2, a VEGFR3, a connexin, or a myostatin. 
     
     
         13 . The method of  claim 11 , wherein the nucleic acid is an antisense nucleic acid specific to an mRNA encoding the protein. 
     
     
         14 . The method of  claim 11 , wherein the nucleic acid is, or encodes, (a) a ribozyme or an miRNA specific to an mRNA encoding the protein, or (b) an aptamer that specifically binds and inhibits a protein that inhibits wound healing. 
     
     
         15 . The method of  claim 11 , wherein the nucleic acid inhibits a naturally occurring miRNA that inhibits wound healing. 
     
     
         16 . The method of  claim 15 , wherein the naturally occurring miRNA inhibits expression of VEGF. 
     
     
         17 . The method of  claim 1 , wherein the nucleic acid is part of a viral vector or a plasmid. 
     
     
         18 . The method of  claim 1 , wherein the reduced pressure is provided by an apparatus that comprises a dressing that contacts the wound site. 
     
     
         19 . The method of  claim 18 , wherein the nucleic acid is on or in the dressing such that the nucleic acid is transmitted to the wound site. 
     
     
         20 . A system for treating a wound at a wound site, comprising:
 a distribution manifold;   a reduced pressure source fluidly connected to said distribution manifold to deliver reduced pressure to the wound site; and   a nucleic acid source fluidly connected to said distribution manifold to deliver nucleic acid to the wound site sufficient to treat the wound.