Compositions and methods for the treatment of autosomal recessive congenital ichthyosis
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. A pharmaceutical composition comprising:
(a) a replication defective herpes simplex virus type 1 (HSV-1) comprising a recombinant HSV-1 genome, wherein the recombinant HSV-1 genome comprises one or more polynucleotides encoding a transglutaminase (TGM) polypeptide; and
(b) a pharmaceutically acceptable excipient.
2. The pharmaceutical composition of claim 1 , 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.
3. The pharmaceutical composition of claim 1 , wherein the TGM polypeptide is a human TGM polypeptide.
4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is suitable for topical, transdermal, subcutaneous, intradermal, or transmucosal administration.
5. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is suitable for topical administration.
6. The pharmaceutical composition of claim 1 , wherein the recombinant HSV-1 genome further comprises one or more polynucleotides encoding a glycoprotein H (gH) polypeptide.
7. The pharmaceutical composition of claim 6 , wherein the gH polypeptide is a wild-type gH polypeptide.
8. The pharmaceutical composition of claim 1 , wherein the recombinant HSV-1 genome further comprises an inactivating mutation in an essential immediate early gene.
9. The pharmaceutical composition of claim 8 , wherein the essential immediate early gene is one or both copies of an infected Cell Protein (ICP) 4 gene.
10. The pharmaceutical composition of claim 8 , wherein the essential immediate early gene is an ICP27 gene.
11. A method of delivering one or more polynucleotides encoding a transglutaminase polypeptide into 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 simplex virus type 1 (HSV-1) comprising a recombinant HSV-1 genome, wherein the recombinant HSV-1 genome comprises the one or more polynucleotides encoding a human transglutaminase (TGM) polypeptide; and
(b) a pharmaceutically acceptable excipient.
12. The method of claim 11 , wherein the subject is a human.
13. The method of claim 11 , wherein the pharmaceutical composition is administered topically, transdermally, subcutaneously, intradermally, or transmucosally to the subject.
14. The method of claim 11 , wherein the pharmaceutical composition is administered topically to the subject.
15. The method of claim 11 , wherein the human TGM polypeptide is selected from the group consisting of a human TGM1 polypeptide, a human TGM2 polypeptide, a human TGM3 polypeptide, a human TGM4 polypeptide, a human TGM5 polypeptide, a human TGM6 polypeptide, and a human TGM7 polypeptide.
16. The method of claim 11 , wherein the one or more cells are one or more cells of the skin.
17. The method of claim 11 , wherein the recombinant HSV-1 genome further comprises one or more polynucleotides encoding a gH polypeptide.
18. The method of claim 17 , wherein the gH polypeptide is a wild-type gH polypeptide.
19. The method of claim 11 , wherein the recombinant HSV-1 genome further comprises an inactivating mutation in an essential immediate early gene.
20. The method of claim 19 , wherein the essential immediate early gene is one or both copies of an ICP4 gene.
21. The method of claim 19 , wherein the essential immediate early gene is an ICP27 gene.