Compositions and methods for the treatment of wounds, disorders, and diseases of the skin

Abstract

The present disclosure relates, in part, to pharmaceutical compositions comprising one or more polynucleotides suitable for enhancing, increasing, augmenting, and/or supplementing the levels of Collagen alpha-1 (VII) chain polypeptide and/or Lysyl hydroxylase 3 polypeptide and/or Keratin type I cytoskeletal 17 polypeptide in a subject. The present disclosure also relates, in part, to pharmaceutical compositions and methods of use for providing prophylactic, palliative, or therapeutic relief of a wound, disorder, or disease of the skin in a subject, including a subject having, or at risk of developing, one or more symptoms of epidermolysis bullosa.

1 - 30 . (canceled) 
     
     
         31 . A pharmaceutical composition, comprising:
 a) a replication-defective herpes simplex virus (HSV) comprising a recombinant herpes simplex virus genome, wherein the recombinant herpes simplex virus genome comprises one or more polynucleotides encoding a transgene; and   b) a pharmaceutically acceptable carrier,   wherein the recombinant herpes simplex virus genome comprises an inactivating mutation in one or both copies of the ICP4 herpes simplex virus gene and an inactivating mutation in the ICP22 herpes simplex virus gene.   
     
     
         32 . The pharmaceutical composition of  claim 31 , wherein the pharmaceutical composition comprises an ointment, paste, cream, suspension, emulsion, fatty ointment, gel, powder, lotion, solution, spray, patch, microneedle array, or inhalant. 
     
     
         33 . The pharmaceutical composition of  claim 31 , wherein the inactivating mutation in one or both copies of the ICP4 herpes simplex virus gene is a deletion of at least a portion of the coding sequence of the ICP4 herpes simplex virus gene. 
     
     
         34 . The pharmaceutical composition of  claim 31 , wherein the inactivating mutation in the ICP22 herpes simplex virus gene is a deletion of at least a portion of the coding sequence of the ICP22 herpes simplex virus gene. 
     
     
         35 . The pharmaceutical composition of  claim 31 , wherein the recombinant herpes simplex virus genome further comprises an inactivating mutation in a herpes simplex virus gene selected from the group consisting of ICP0, ICP27, ICP47, tk, UL41, and UL55. 
     
     
         36 . The pharmaceutical composition of  claim 31 , wherein the replication-defective HSV has reduced cytotoxicity as compared to a wild-type herpes simplex virus. 
     
     
         37 . The pharmaceutical composition of  claim 31 , wherein the pharmaceutical composition is suitable for delivery to a subject. 
     
     
         38 . The pharmaceutical composition of  claim 37 , wherein the replication-defective HSV is suitable for delivering to and expressing the one or more polynucleotides encoding the transgene in one or more target cells of the subject. 
     
     
         39 . The pharmaceutical composition of  claim 38 , wherein the subject is a human. 
     
     
         40 . The pharmaceutical composition of  claim 31 , wherein the one or more polynucleotides encoding the transgene is in one or both of the ICP4 viral gene loci. 
     
     
         41 . The pharmaceutical composition of  claim 31 , wherein the recombinant herpes simplex virus genome is a recombinant HSV-1 genome. 
     
     
         42 . A method of delivering a transgene to a subject, the method comprising administering to the subject a pharmaceutical composition comprising:
 a) a replication-defective herpes simplex virus (HSV) comprising a recombinant herpes simplex virus genome, wherein the recombinant herpes simplex virus genome comprises one or more polynucleotides encoding a transgene; and   b) a pharmaceutically acceptable carrier,   wherein the recombinant herpes simplex virus genome comprises an inactivating mutation in one or both copies of the ICP4 herpes simplex virus gene and an inactivating mutation in the ICP22 herpes simplex virus gene.   
     
     
         43 . The method of  claim 42 , wherein the pharmaceutical composition comprises an ointment, paste, cream, suspension, emulsion, fatty ointment, gel, powder, lotion, solution, spray, patch, microneedle array, or inhalant. 
     
     
         44 . The method of  claim 42 , wherein the inactivating mutation in one or both copies of the ICP4 herpes simplex virus gene is a deletion of at least a portion of the coding sequence of the ICP4 herpes simplex virus gene. 
     
     
         45 . The method of  claim 42 , wherein the inactivating mutation in the ICP22 herpes simplex virus gene is a deletion of at least a portion of the coding sequence of the ICP22 herpes simplex virus gene. 
     
     
         46 . The method of  claim 42 , wherein the pharmaceutical composition is administered by via inhalation, transdermal administration, subcutaneous injection, intradermal injection, intravenous injection, intra-arterial injection, intramuscular injection, intracardiac injection, intraosseous injection, intraperitoneal injection, transmucosal administration, vaginal administration, intravitreal administration, intra-articular administration, peri-articular administration, local administration, epicutaneous administration, topical administration, or a combination thereof. 
     
     
         47 . The method of  claim 42 , wherein the replication-defective HSV has reduced cytotoxicity as compared to a wild-type herpes simplex virus. 
     
     
         48 . The method of  claim 42 , wherein the subject is a human.