Compositions and methods for the treatment of wounds, disorders, and diseases of the skin
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. A method of delivering a transgene to the skin of 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 the 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;
wherein the pharmaceutical composition is topically or transdermally administered to the subject; and
wherein the pharmaceutical composition is administered to one or more areas of the subject affected by a wound, disorder, or disease of the skin.
2. The method of claim 1 , wherein the recombinant herpes simplex virus genome further comprises an inactivating mutation in the ICP22 herpes simplex virus gene, and wherein the inactivating mutation is a deletion of at least a portion of the coding sequence of the ICP22 herpes simplex virus gene.
3. The method of claim 1 , wherein the pharmaceutical composition is topically administered to the subject.
4. The method of claim 1 , wherein the subject is a human.
5. The method of claim 1 , wherein the disease or disorder of the skin is selected from the group consisting of epidermolysis bullosa, skin cancer, psoriasis, lichen planus, lupus, rosacea, eczema, cutaneous candidiasis, cellulitis, impetigo, decubitus ulcers, erysipelas, ichthyosis vulgaris, dermatomyositis, acrodermatitis, stasis dermatitis, Netherton's syndrome, epidermolysis bullosa simplex, autosomal recessive congenital ichthyosis, xeroderma pigmentosa, and pemphigoid.
6. The method of claim 1 , 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 epidermis and/or dermis of the subject.
7. The method of claim 1 , wherein 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.
8. A method of delivering a transgene to the skin of 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 the 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 ICP 4 herpes simplex virus gene;
wherein the pharmaceutical composition comprises an ointment, paste, cream, suspension, emulsion, fatty ointment, gel, powder, lotion, solution, spray, patch, or microneedle array; and
wherein pharmaceutical composition is administered to one or more areas of the subject affected by a wound, disorder, or disease of the skin.
9. The method of claim 8 , wherein the subject is a human.
10. The method of claim 8 , wherein the disease or disorder of the skin is selected from the group consisting of epidermolysis bullosa, skin cancer, psoriasis, lichen planus, lupus, rosacea, eczema, cutaneous candidiasis, cellulitis, impetigo, decubitus ulcers, erysipelas, ichthyosis vulgaris, dermatomyositis, acrodermatitis, stasis dermatitis, Netherton's syndrome, epidermolysis bullosa simplex, autosomal recessive congenital ichthyosis, xeroderma pigmentosa, and pemphigoid.
11. The method of claim 8 , 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 epidermis and/or dermis of the subject.
12. The method of claim 8 , 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, ICP22, ICP27, ICP47, tk, UL41, and UL55.
13. The method of claim 8 , wherein the recombinant herpes simplex virus genome further comprises an inactivating mutation in the ICP22 herpes simplex virus gene.
14. The method of claim 13 , 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.
15. The method of claim 8 , wherein the pharmaceutical composition comprises a gel.
16. The method of claim 15 , wherein the gel comprises hydroxypropyl methylcellulose.
17. The method of claim 8 , wherein the pharmaceutical composition comprises a suspension.
18. The method of claim 8 , wherein the pharmaceutical composition comprises a solution.
19. The method of claim 8 , wherein the pharmaceutical composition is administered topically, transdermally, subcutaneously, or intradermally to the subject.
20. The method of claim 8 , wherein the pharmaceutical composition is administered topically to the subject.