Compositions and methods for the treatment of autosomal recessive congenital ichthyosis

Abstract

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a transglutaminase (TGM) polypeptide (e.g., a Transglutaminase-1 (TGM1) polypeptide); viruses comprising the recombinant nucleic acids; compositions comprising the recombinant nucleic acids and/or viruses; methods of their use; and articles of manufacture or kits thereof.

1 .- 30 . (canceled) 
     
     
         31 . A pharmaceutical composition comprising:
 (a) a replication defective herpes virus comprising a recombinant herpes virus genome, wherein the recombinant herpes virus genome comprises one or more polynucleotides encoding a transglutaminase (TGM) polypeptide; and   (b) a pharmaceutically acceptable excipient.   
     
     
         32 . The pharmaceutical composition of  claim 31 , wherein the recombinant herpes virus genome is selected from the group consisting of a recombinant herpes simplex virus genome, a recombinant varicella zoster virus genome, a recombinant human cytomegalovirus genome, a recombinant herpesvirus 6A genome, a recombinant herpesvirus 6B genome, a recombinant herpesvirus 7 genome, a recombinant Kaposi's sarcoma-associated herpesvirus genome, and any derivatives thereof. 
     
     
         33 . The pharmaceutical composition of  claim 31 , wherein the replication defective herpes virus is a replication defective herpes simplex virus type-1 (HSV-1). 
     
     
         34 . The pharmaceutical composition of  claim 31 , wherein the TGM polypeptide is selected from the group consisting of a TGM1 polypeptide, a TGM2 polypeptide, a TGM3 polypeptide, a TGM4 polypeptide, a TGM5 polypeptide, a TGM6 polypeptide, and a TGM7 polypeptide. 
     
     
         35 . The pharmaceutical composition of  claim 31 , wherein the TGM polypeptide is a human TGM polypeptide. 
     
     
         36 . The pharmaceutical composition of  claim 31 , wherein the replication defective herpes virus has reduced cytotoxicity as compared to a corresponding wild-type herpes virus. 
     
     
         37 . The pharmaceutical composition of  claim 31 , wherein the replication defective herpes virus is selected from the group consisting of a herpes simplex virus, a varicella zoster virus, a human cytomegalovirus, a herpesvirus 6A, a herpesvirus 6B, a herpesvirus 7, and a Kaposi's sarcoma-associated herpesvirus. 
     
     
         38 . The pharmaceutical composition of  claim 31 , wherein the pharmaceutical composition is suitable for topical, transdermal, subcutaneous, intradermal, administration. 
     
     
         39 . The pharmaceutical composition of  claim 31 , wherein the pharmaceutical composition is suitable for topical administration. 
     
     
         40 . A method of enhancing, increasing, augmenting, or supplementing expression of one or more polynucleotides encoding a transglutaminase (TGM) polypeptide in one or more cells of a subject, the method comprising administering to the subject an effective amount of a pharmaceutical composition comprising:
 (a) a replication defective herpes virus comprising a recombinant herpes virus genome, wherein the recombinant herpes virus genome comprises the one or more polynucleotides encoding the TGM polypeptide; and   (b) a pharmaceutically acceptable excipient.   
     
     
         41 . The method of  claim 40 , wherein the subject is a human. 
     
     
         42 . The method of  claim 40 , wherein the pharmaceutical composition is administered topically, transdermally, subcutaneously, intradermally, or transmucosally to the subject. 
     
     
         43 . The method of  claim 40 , wherein the pharmaceutical composition is administered topically to the subject. 
     
     
         44 . The method of  claim 40 , wherein the recombinant herpes virus genome is selected from the group consisting of a recombinant herpes simplex virus genome, a recombinant varicella zoster virus genome, a recombinant human cytomegalovirus genome, a recombinant herpesvirus 6A genome, a recombinant herpesvirus 6B genome, a recombinant herpesvirus 7 genome, a recombinant Kaposi's sarcoma-associated herpesvirus genome, and any derivatives thereof. 
     
     
         45 . The method of  claim 40 , wherein the replication defective herpes virus is a replication defective herpes simplex virus type-1 (HSV-1). 
     
     
         46 . The method of  claim 40 , wherein the TGM polypeptide is selected from the group consisting of a TGM1 polypeptide, a TGM2 polypeptide, a TGM3 polypeptide, a TGM4 polypeptide, a TGM5 polypeptide, a TGM6 polypeptide, and a TGM7 polypeptide. 
     
     
         47 . The method of  claim 40 , wherein the TGM polypeptide is a human TGM polypeptide. 
     
     
         48 . The method of  claim 40 , wherein the replication defective herpes virus has reduced cytotoxicity as compared to a corresponding wild-type herpes virus. 
     
     
         49 . The method of  claim 40 , wherein the replication defective herpes virus is selected from the group consisting of a herpes simplex virus, a varicella zoster virus, a human cytomegalovirus, a herpesvirus 6A, a herpesvirus 6B, a herpesvirus 7, and a Kaposi's sarcoma-associated herpesvirus. 
     
     
         50 . The method of  claim 40 , wherein the one or more target cells are one or more cells of the skin.