Recombinant nucleic acids encoding cosmetic protein(s) for aesthetic

Inventors

Krishnan, Suma • PARRY, Trevor • Agarwal, Pooja

Assignees

Krystal Biotech Inc

Abstract

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding one or more cosmetic proteins (e.g., one or more human collagen proteins); viruses comprising the recombinant nucleic acids; compositions (e.g., cosmetic formulations) comprising the recombinant nucleic acids and/or viruses; methods of their use; and articles of manufacture or kits thereof.

Core Innovation

The invention relates to a composition for topical, transdermal, superficial, or intradermal administration that includes a replication defective herpes simplex virus type 1 (HSV-1) comprising a recombinant HSV-1 genome and an excipient. The recombinant HSV-1 genome comprises a first polynucleotide encoding a first protein selected from collagen proteins, fibronectin proteins, elastin proteins, lumican proteins, vitronectin proteins, vitronectin receptor proteins, laminin proteins, neuromodulator proteins, and fibrillin proteins, and the genome includes an inactivating mutation in one or both copies of the ICP4 herpes simplex virus gene. The genome does not comprise a polynucleotide encoding a Collagen alpha-1 (VII) chain (COL7) polypeptide.

In the described embodiments, the recombinant HSV-1 genome can include one or more additional inactivating mutations in herpes simplex virus genes selected from ICP0, ICP22, ICP27, ICP47, thymidine kinase (tk), UL41, and UL55. The disclosed subject matter also includes recombinant herpes viral genomes and vectors for expressing cosmetic/dermal extracellular matrix proteins, including recombinant HSV-1 genome embodiments having multiple HSV-gene inactivations for attenuation and replication defect, and reduced cytotoxicity, with insertion of transgene polynucleotides into HSV gene loci.

The disclosed subject matter is directed to enhancing dermal extracellular-matrix (ECM) and collagen levels and improving skin aging signs, including superficial wrinkles, superficial depressions, sagging, and UV damage, after administration. The compositions are described as cosmetic skin-care compositions formulated with the claimed replication defective HSV-1 and an excipient, and are associated with administration to skin compartments such as epidermis, dermis, and subcutis. The stated embodiment emphasizes expression of exogenous human collagen mRNA and protein with localization relevant to skin-equivalent organotypic cultures and dermal extracellular matrix after topical or intradermal delivery.

Claims Coverage

The consolidated content includes two independent claims: one composition claim and one method claim. Across these independent claims, the inventive structure centers on a replication defective HSV-1 recombinant genome with an ICP4 inactivating mutation, a selected ECM/related protein payload, exclusion of a COL7-encoding polynucleotide, and specified administration routes.

Claim coverage centers on a replication defective HSV-1 recombinant genome designed to express a defined group of extracellular-matrix/related proteins while carrying an ICP4 inactivating mutation and lacking a COL7-encoding polynucleotide; the coverage applies to specified administration routes and is directed to improving skin condition, quality, and/or appearance.

Stated Advantages

Documented Applications