Methods and Compositions for Treating Keratin Hyperproliferation Disorders

Abstract

A method for keratin hyperproliferation disorders such as corns, calluses, or keratosis pilaris (KP) by administering to a subject experiencing the disorder a therapeutically effective amount of an RNA sequence which inhibits expression of a gene encoding for a keratin selected from the group consisting of K6a, K6b, K16, K17, and combinations thereof.

1 . A method of treating or preventing a hyperproliferation skin disorder in a subject, 
       comprising:
 administering to the subject a therapeutically effective amount of an RNA sequence which inhibits expression of a gene encoding for a keratin selected from the group consisting of K6a, K6b, K16, K17, and combinations thereof. 
 
     
     
         2 . The method of  claim 1 , wherein the hyperproliferation skin disorder is selected from the group consisting of keratosis pilaris, calluses, corns, psoriasis, keratosis follicularis, pityriasis rubra pilaris, and Clouston syndrome. 
     
     
         3 . The method of  claim 2 , wherein the hyperproliferation skin disorder is keratosis pilaris. 
     
     
         4 . The method of  claim 2 , wherein the hyperproliferation skin disorder is a callus. 
     
     
         5 . The method of  claim 2 , wherein the hyperproliferation skin disorder is a corn. 
     
     
         6 . The method of  claim 1 , wherein the RNA sequence is a small interfering RNA. 
     
     
         7 . The method of  claim 1 , wherein the subject's overexpressed gene encodes keratin 6a (K6a). 
     
     
         8 . The method of  claim 1 , wherein the subject's overexpressed gene encodes keratin 6b (K6b). 
     
     
         9 . The method of  claim 1 , wherein the subject's overexpressed gene encodes keratin 16 (K16). 
     
     
         10 . The method of  claim 1 , wherein the subject's overexpressed gene encodes keratin 17 (K17). 
     
     
         11 . The method of  claim 6 , wherein the RNA sequence is a member selected from the group consisting of: SEQ. ID NO: 2, SEQ. ID NO: 4, SEQ. ID NO: 6, SEQ. ID NO: 8, SEQ. ID NO: 10, SEQ. ID NO: 12, SEQ. ID NO: 14, SEQ. ID NO: 16, SEQ. ID NO: 18, SEQ. ID NO: 20, SEQ. ID NO: 22, SEQ. ID NO: 24, SEQ. ID NO: 26, SEQ. ID NO: 28, SEQ. ID NO: 30, SEQ. ID NO: 32, SEQ. ID NO: 34, SEQ. ID NO: 36, SEQ. ID NO: 38, SEQ. ID NO; 40, SEQ. ID NO: 42, SEQ. ID NO: 44, SEQ. ID NO: 46, SEQ. ID NO: 48, SEQ. ID NO: 50, SEQ. ID NO: 52, SEQ. ID NO: 54, SEQ. ID NO: 56, SEQ. ID NO: 58, SEQ. ID NO: 60, SEQ. ID NO: 62, SEQ. ID NO: 64, SEQ. ID NO: 66, SEQ. ID NO: 68, SEQ. ID NO: 70, SEQ. ID NO: 72, SEQ. ID NO: 74, SEQ. ID NO: 76, SEQ. ID NO: 78, SEQ. ID NO: 80, and mixtures thereof. 
     
     
         12 . The method of  claim 1 , wherein the siRNA sequence is administered as double stranded RNA. 
     
     
         13 . The method of  claim 1 , wherein the siRNA sequence is administered as a short hairpin RNA. 
     
     
         14 . The method of  claim 1 , wherein the RNA sequence has a length of about 15 to about 31 nucleotides. 
     
     
         15 . The method of  claim 1 , wherein the RNA sequence is administered transdermally. 
     
     
         16 . The method of  claim 15 , wherein the transdermal administration includes formulations and processes selected from the group consisting of: a lotion, a cream, a gel, an ointment, a paste, a transdermal patch, a liposome, iontophoresis, electroporation, sonophoresis, or combinations thereof. 
     
     
         17 . The method of  claim 1 , wherein the RNA sequence is administered by intradermal injection. 
     
     
         18 . The method of  claim 17 , wherein the intradermal injection is accomplished using dissolvable needles. 
     
     
         19 . The method of  claim 1 , wherein the RNA sequence is administered in a therapeutically effective amount of from about 0.1 mg to about 10 mg. 
     
     
         20 . The method of  claim 1 , wherein the RNA sequence contains at least one modified nucleotide. 
     
     
         21 . The method of  claim 1 , wherein the RNA sequence is administered in combination with a therapeutically effective amount of a compound selected from the group consisting of corticosteroid, lanolin, aloe vera, urea, propylene glycol, α-hydroxy acids, lactic acid, salicylic acid, vitamin D 3  and its derivatives, vitamin A and retinoids, levothyroxin, NSAIDS, cyclosporine, methotrexate sodium, anthralin, acitretin, tazarotene, coal tar, botulinum toxin, topical anesthetics, antihistamine, and combinations thereof. 
     
     
         22 . The method of  claim 1 , wherein the inhibited gene encodes for a mutated keratin. 
     
     
         23 . The method of  claim 1 , wherein the inhibited gene encodes a wildtype keratin. 
     
     
         24 . The method of  claim 20 , wherein the RNA sequence inhibits expression of both mutated and wildtype keratin genes. 
     
     
         25 . The method of  claim 1 , wherein the inhibited gene encodes the K6b keratin and the RNA sequence is a member selected from the group consisting of: SEQ. ID NO: 22, SEQ. ID NO: 24, SEQ. ID NO: 26, SEQ. ID NO: 28, SEQ. ID NO: 30, SEQ. ID NO: 32, SEQ. ID NO: 34, SEQ. ID NO: 36, SEQ. ID NO: 38, SEQ. ID NO: 40, and combinations thereof. 
     
     
         26 . The method of  claim 1 , wherein the inhibited gene encodes the K16 keratin and the RNA sequence is a member selected from the group consisting of: SEQ. ID NO: 42, SEQ. ID NO: 44, SEQ. ID NO: 46, SEQ. ID NO: 48, SEQ. ID NO: 50, SEQ. ID NO: 52, SEQ. ID NO: 54, SEQ. ID NO: 56, SEQ. ID NO: 58, SEQ. ID NO: 60, and combinations thereof. 
     
     
         27 . The method of  claim 1 , wherein the inhibited gene encodes the K17 keratin and the RNA sequence is a member selected from the group consisting of: SEQ. ID NO: 62, SEQ. ID NO: 64, SEQ. ID NO: 66, SEQ. ID NO: 68, SEQ. ID NO: 70, SEQ. ID NO: 72, SEQ. ID NO: 74, SEQ. ID NO: 76, SEQ. ID NO: 78, SEQ. ID NO: 80, and combinations thereof