Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor

Abstract

A method for the direct treatment towards the specific sites of a disease is disclosed. This method is based on the delivery of proteins by catheterization to discrete blood vessel segments using genetically modified or normal cells or other vector systems. Endothelial cells expressing recombinant therapeutic agent or diagnostic proteins are situated on the walls of the blood vessel or in the tissue perfused by the vessel in a patient. This technique, provides for the transfer of cells or vectors and expression of recombinant genes in vivo and allows the introduction of proteins of therapeutic or diagnostic value for the treatment of diseases.

1 - 17 . (canceled)  
   
   
       18 . A kit for treating a disease in a patient, comprising: 
 a catheter comprising a body and balloon element adapted to be inserted into a blood vessel of said patient and being expansible against the walls of said vessel so as to hold said catheter body in place; and    a physiologically acceptable solution comprising cells,    wherein said catheter body includes means for delivering said composition into said blood vessel.    
   
   
       19 . The kit of  claim 18 , wherein said catheter body comprises two spaced balloon elements, adapted to be inserted in a blood vessel and both being expansible against the wall of the blood vessel, for providing a chamber in said blood vessel and so as to hold said body in place, and where the means for delivering the composition into the blood vessel is situated in between the balloon elements.  
   
   
       20 . The kit of  claim 18 , wherein the cells are normal (untransformed) cells.  
   
   
       21 . The kit of  claim 18 , wherein the cells are transformed cells.  
   
   
       22 . The kit of  claim 18 , wherein the means for delivering the composition into the blood vessel comprises a plurality of pores.  
   
   
       23 . The kit of  claim 18 , wherein the number of pores is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12.  
   
   
       24 . The kit of  claim 18 , wherein the cells are endothelial cells, smooth muscle cells, fibroblasts, monocytes, macrophages, or parenchymal cells.  
   
   
       25 . The kit of  claim 18 , wherein the cells produce a protein which has a therapeutic or diagnostic effect in the patient.  
   
   
       26 . The kit of  claim 18 , wherein the cells produce an angiogenic factor.  
   
   
       27 . The kit of  claim 18 , wherein the cells are glucose-responsive insulin-secreting cells.  
   
   
       28 . The kit of  claim 18 , wherein the cells produce a toxin.  
   
   
       29 . The kit of  claim 18 , wherein the composition is stored in liquid nitrogen.  
   
   
       30 . The kit of claim  1 , wherein the catheter is a catheter as described in U.S. Pat. No. 4,636,195.  
   
   
       31 . The kit of  claim 18 , wherein the kit further comprises a guidewire.  
   
   
       32 . The kit of  claim 18 , wherein the composition further comprises heparin, poly-L-lysine, polybrene, dextran sulfate, a polycationic material, or a bivalent antibody.  
   
   
       33 . The kit of  claim 21 , wherein the cell comprises a nucleic acid sequence encoding tPA, urokinase, streptokinase, acidic fibroblast growth factor, basic fibroblast growth factor, tumor necrosis factor α, tumor necrosis factor β, transforming growth factor α, transforming growth factor β, atrial natriuretic factor, platelet-derived growth factor, endothelian, insulin, diphtheria toxin, pertussis toxin, cholera toxin, soluble CD4, a growth hormone, a marker protein, or derivatives thereof.  
   
   
       34 . A kit for treating a disease in a patient in need thereof, comprising: 
 a) a medical device for insertion into a blood vessel; and    b) an antisense agent which is complementary to a DNA or mRNA encoded by a gene in said patient.    
   
   
       35 . The kit of  claim 34 , wherein the antisense agent is complementary to the 5′ untranslated region of the mRNA.  
   
   
       36 . The kit of  claim 34 , wherein the antisense agent is complementary to the coding region of the mRNA.  
   
   
       37 . The kit of  claim 34 , wherein the antisense agent is complementary to the 3′ untranslated region of the mRNA.  
   
   
       38 . The kit of  claim 34 , wherein the antisense agent is a synthetic oligonucleotide.  
   
   
       39 . The kit of  claim 34 , wherein the antisense agent is antisense DNA.  
   
   
       40 . The kit of  claim 34 , wherein the medical device is a catheter.  
   
   
       41 . The kit of  claim 34 , wherein the medical device is a syringe and needle.  
   
   
       42 . The kit of  claim 34 , wherein the gene encodes an angiogenic factor.  
   
   
       43 . The kit of  claim 34 , wherein the antisense agent is in solution.  
   
   
       44 . The kit of  claim 34 , wherein the antisense agent is a plasmid which expresses the revise complement of the gene.  
   
   
       45 . The kit of  claim 34 , wherein the gene encodes a protein that induces angiogenesis.