Methods for coating stents with DNA and expression of recombinant genes from DNA coated stents in vivo

Abstract

The present invention describes DNA coated stents and methods of using the same to treat or prevent vascular diseases, such as restenosis.

1 - 56 . (canceled)  
     
     
         57 . A device for delivery of a therapeutic agent, comprising an implantable device coated with a composition comprising a polymer and a DNA encoding a therapeutically useful protein.  
     
     
         58 . The device of  claim 57 , wherein the implantable device is a stent.  
     
     
         59 . The device of  claim 57 , wherein the implantable device is composed of stainless steel.  
     
     
         60 . The device of  claim 57 , wherein the therapeutically useful protein is a gene encoding an antiplatelet agent, anticoagulant agent, antimitotic agent, antioxidant, antimetabolite agent, or anti-inflammatory agent.  
     
     
         61 . The device of  claim 60 , wherein the therapeutically useful protein inhibits the proliferation of cells.  
     
     
         62 . The device of  claim 61 , wherein the therapeutically useful protein is thymidine kinase, p16, p21, p27, p57, retinoblastoma or cytosine deaminase.  
     
     
         63 . The device of  claim 62 , wherein the therapeutically useful protein is thymidine kinase or cytosine deaminase.  
     
     
         64 . The device of  claim 57 , wherein the stent is coated with about 50 μg to about 5 mg of DNA.  
     
     
         65 . The device of  claim 57 , wherein the polymer comprises fibrin.  
     
     
         66 . The device of  claim 57 , wherein the device is coated with a polymer matrix.  
     
     
         67 . The implantable device of  claim 57 , wherein the device is coated with a polymer selected from the group consisting of poly(ethylene terephthalate), polyacetal, and poly(ethylene oxide)/poly(butylene terephthalate) copolymer.  
     
     
         68 . The implantable device of  claim 57 , wherein the DNA is naked DNA.  
     
     
         69 . The implantable device of  claim 57 , wherein the DNA is incorporated into a vector.  
     
     
         70 . The implantable device of  claim 69 , wherein the vector is selected from the group consisting of shuttle vectors, expression vectors, retroviral vectors, adenoviral vectors, adeno-associated vectors and liposomes.  
     
     
         71 . The implantable device of  claim 66 , wherein the polymer matrix is formed from an aqueous suspension of DNA and liquid monomeric matrix.  
     
     
         72 . The implantable device of  claim 57 , wherein the DNA comprises an sm 22.alpha. promoter operatively linked to the DNA encoding the therapeutically useful protein.  
     
     
         73 . The implantable device of  claim 57 , wherein the therapeutically useful protein is a fusion protein.  
     
     
         74 . The implantable device of  claim 58 , wherein the stent is an intravascular stent.  
     
     
         75 . The implantable device of  claim 57 , wherein the device is coated with a polymer matrix wherein said DNA is uniformly dispersed within said matrix.  
     
     
         76 . An implantable device comprising a stent coated with a composition comprising a polymer and a DNA encoding a therapeutically useful protein.  
     
     
         77 . The implantable device of  claim 76 , wherein the therapeutically useful protein is an antiplatelet agent, anticoagulant agent, antimitotic agent, antioxidant, antimetabolite agent, or anti-inflammatory agent.  
     
     
         78 . The implantable device of  claim 76 , wherein the therapeutically useful protein inhibits the proliferation of cells.  
     
     
         79 . The implantable device of  claim 76 , wherein the therapeutically useful protein is thymidine kinase, p16, p21, p27, p57, retinoblastoma or cytosine deaminase.  
     
     
         80 . The implantable device of  claim 76 , wherein the stent is coated with about 50 μg to about 5 mg of DNA.  
     
     
         81 . The implantable device of  claim 75 , wherein the polymer is selected from the group consisting of poly(ethylene terephthalate), polyacetal, and poly(ethylene oxide)/poly(butylene terephthalate) copolymer.