Ribozyme therapy for the treatment of proliferative skin and eye diseases

Abstract

As an effective therapy for proliferative skin and eye diseases such as psoriasis and proliferative diabetic retinopathy, this invention provides ribozymes and ribozyme delivery systems which cleave RNA encoding cytokines involved in inflammation, matrix metalloproteinases, a cyclin, a cell-cycle dependent kinase, a growth factor, or a reductase.

1 - 105 . (canceled)  
     
     
         106 . A method of treating a proliferative skin disease or scarring, comprising administering to a patient a therapeutically effective amount of a ribozyme which cleaves RNA encoding a cyclin PCNA, such that said proliferative skin disease or scarring is treated, said RNA comprising SEQ ID NO: 4145, wherein the binding arms of said ribozyme bind to SEQ ID NO:4145.  
     
     
         107 . The method of  claim 106 , wherein said administration is local.  
     
     
         108 . The method of  claim 106 , wherein said scar is a keloid.  
     
     
         109 . The method of  claim 106 , wherein said scar is an adhesion.  
     
     
         110 . The method of  claim 106 , wherein said scar is a hypertrophic scar.  
     
     
         111 . The method of  claim 106 , wherein said scar is a hypertrophic burn scar.  
     
     
         112 . The method of  claim 106 , wherein said scar is caused by trauma.  
     
     
         113 . The method of  claim 106 , wherein said ribozyme is a hammerhead or hairpin ribozyme.  
     
     
         114 . The method of  claim 106 , wherein said ribozyme is formulated within a solution.  
     
     
         115 . The method of  claim 106  wherein said ribozyme is formulated along with a lipid.  
     
     
         116 . The method of  claim 115 , wherein said lipid is DOTAP: cholesterol.  
     
     
         117 . The method of  claim 106 , wherein said ribozyme is formulated with ribonuclease inhibitors.  
     
     
         118 . The method of  claim 117 , wherein said ribonuclease inhibitor is a reducing agent.  
     
     
         119 . The method of  claim 118 , wherein the reducing agent is dithiothreitol.  
     
     
         120 . The method of  claim 117 , wherein said ribonuclease inhibitor is a detergent.  
     
     
         121 . The method of  claim 120 , wherein the detergent is sodium dodecyl sulfate.  
     
     
         122 . The method of  claim 117 , wherein said ribonuclease inhibitor is vanidyl nucleotides.  
     
     
         123 . The method of  claim 117 , wherein said ribonuclease inhibitor is aurin tricarboxcylic acid.  
     
     
         124 . The method of  claim 117 , wherein said ribonuclease inhibitor is hydrogen peroxide.  
     
     
         125 . The method of  claim 117 , wherein said ribonuclease inhibitor is an RNA decoy.  
     
     
         126 . The method according to claim  97  wherein said RNA decoy is a tRNA.  
     
     
         127 . The method of  claim 106 , wherein said ribozyme comprises ribonucleic acids.  
     
     
         128 . The method of  claim 106 , wherein said ribozyme comprises deoxyribonucleic acids and ribonucleic acids.  
     
     
         129 . The method of  claim 106 , wherein said ribozyme comprises nucleic acids having phosphothioate linkages.  
     
     
         130 . The method of  claim 106 , wherein said ribozyme is administered topically.  
     
     
         131 . The method of  claim 106 , wherein said ribozyme is administered intradermally.  
     
     
         132 . The method of  claim 106 , wherein said ribozyme is formulated within a cream, ointment or lotion.  
     
     
         133 . The method of  claim 106 , wherein said ribozyme comprises a sequence selected from the group consisting of SEQ ID NOS: 4383 and 4385.  
     
     
         134 . The method of  claim 133 , wherein said sequence is SEQ ID NO: 4385.  
     
     
         135 . The method of  claim 106 , wherein said proliferative skin disease is psoriasis.  
     
     
         136 . The method of  claim 106 , wherein said proliferative skin disease is dermatitis.  
     
     
         137 . The method of  claim 106 , wherein said proliferative skin disease is keratosis.  
     
     
         138 . The method of  claim 106 , wherein said proliferative skin disease is basal cell carcinoma.  
     
     
         139 . The method of  claim 106 , wherein said proliferative skin disease is viral or seborrheic wart.