Viral vectors for cosmetic administration

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 or elastin 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.

Description

Attorney Docket No.: 10423-2600083 VIRAL VECTORS FOR COSMETIC ADMINISTRATIONCROSS REFERENCE TO RELATED APPLICATION

[0001] This application claims the priority benefit of United States Provisional Application No. 63 / 747,666, filed January 21, 2025, the disclosure of which is hereby incorporated by reference in its entirety.SUBMISSION OF SEQUENCE LISTING ON ASCII TEXT FILE

[0002] The Sequence Listing associated with this application is filed in electronic format via Patent Center and is hereby incorporated by reference into the specification in its entirety. The name of the file containing the Sequence Listing is 2407626. xml. The size of the file is 266,479 bytes, and the file was created on January 21, 2025.FIELD OF THE INVENTION

[0003] The present disclosure relates, in part, to recombinant nucleic acids comprising one or more polynucleotides encoding one or more cosmetic proteins (e.g., one or more human collagen proteins, one or more human elastin proteins, and / or one or more human hyaluronan synthase proteins); to viruses comprising the recombinant nucleic acids; to compositions (e.g., cosmetic formulations) comprising the recombinant nucleic acids and / or viruses; to methods of their use (e.g. administration to the decollete of a subject); and to articles of manufacture or kits thereof.BACKGROUND

[0004] Skin, like all organs in the human body, undergoes sequential and often cumulative alterations with the passage of time. Aging of the skin occurs as the result of numerous factors, including inherent changes within the skin, the effects of gravity and facial muscles acting on the skin, soft tissue loss or shift, and loss of tissue elasticity. Interestingly, the “aged” phenotype of skin may be accelerated by environmental factors, most notably, chronic exposure to ultraviolet irradiation (e.g., from the sun). Clinically, the aged phenotype of skin may be described as wrinkled, sagging, and / or generally less elastic and resilient than its youthful counterpart, although variations within this phenotype exist between natural, chronological aging and photoaging.

[0005] The dermal extracellular matrix (ECM) comprises the bulk of skin and confers both strength and resiliency. Collagen, a major component of the connective tissue providing support to the skin, decreases as a person ages. In aged skin, collagen fibrils display high levels16A97680.DOCXAttorney Docket No.: 10423-2600083 of degradation and fragmentation, and are replenished by dermal fibroblasts at diminishing rates. These degraded and fragmented collagen bundles become looser and lose strength (disrupting the structural organization of the dermal ECM), and inextricably leads to an “aged” manifestation of the skin.

[0006] Numerous skincare products have been developed for improving the appearance of human skin. Wrinkles and skin folds are commonly treated with dermal and subdermal injections of aesthetic facial fillers; however, such a superficial approach does not address the structural changes underlying skin aging, in particular, the damage or loss of collagen. Thus, there exists a clear need for alternative strategies to supplement, strengthen, or replace dermal ECM components (e.g., human collagen, human elastin, and / or human hyaluronan synthase) in individuals desiring to combat or reverse the physiological effects of skin aging.

[0007] All references cited herein, including patent applications, patent publications, nonpatent literature, and NCBI / UniProtKB / Swiss-Prot Accession numbers are herein incorporated by reference in their entirety, as if each individual reference were specifically and individually indicated to be incorporated by reference.BRIEF SUMMARY

[0008] In order to meet these and other needs, provided herein are recombinant nucleic acids (e.g., recombinant herpes viral genomes) encoding one or more cosmetic proteins for use in viruses (e.g., herpes viruses), compositions, formulations, medicaments, and / or methods for aesthetic / cosmetic applications (e.g., treating wrinkles of the decollete).

[0009] Accordingly, certain aspects of the present disclosure relate to a recombinant herpes virus genome comprising a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein. In some embodiments, the recombinant herpes virus genome comprises two or more copies of the first polynucleotide. In some embodiments, the recombinant herpes virus genome is replication competent. In some embodiments, the recombinant herpes virus genome is replication defective. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes virus genome is selected from 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. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes virus genome is a recombinant herpes simplex virus genome. In some embodiments, the recombinant herpes simplex virus26A97680.DOCXAttorney Docket No.: 10423-2600083 genome is a recombinant herpes simplex virus type 1 (HSV-1) genome, a recombinant herpes simplex virus type 2 (HSV-2) genome, or any derivatives thereof.

[0010] In some embodiments, the recombinant herpes simplex virus genome is a recombinant herpes simplex virus type 1 (HSV-1) genome. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation. In some embodiments that may be combined with any of the preceding embodiments, the inactivating mutation is in a herpes simplex virus gene. In some embodiments, the inactivating mutation is a deletion of the coding sequence of the herpes simplex virus gene. In some embodiments, the herpes simplex virus gene is selected from Infected Cell Protein (ICP) 0, ICP4, ICP22, ICP27, ICP47, thymidine kinase (tk), Long Unique Region (UL) 41, and UL55. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in one or both copies of the ICP4 gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP22 gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the UL41 gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in one or both copies of the ICPO gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP27 gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the UL55 gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the Joint region. In some embodiments, the recombinant herpes simplex virus genome comprises a deletion of the Joint region. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within one or both of the ICP4 viral gene loci.

[0011] In some embodiments that may be combined with any of the preceding embodiments, the first cosmetic protein is selected from a first collagen protein, a first fibronectin protein, a first elastin protein, a first lumican protein, a first vitronectin protein, a first vitronectin receptor protein, a first laminin protein, a first neuromodulator protein, a first fibrillin protein, and a first hyaluronan synthase protein. In some embodiments that may be 36A97680.DOCXAttorney Docket No.: 10423-2600083 combined with any of the preceding embodiments, the first cosmetic protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21, 53-64, and 68-70. In some embodiments, the first cosmetic protein is a structural extracellular matrix protein (e.g., a collagen protein, an elastin protein, a fibronectin protein, a laminin protein, a fibrillin protein, etc. . In some embodiments, the first cosmetic protein is a collagen protein, an elastin protein, a fibronectin protein, a laminin protein, or a hyaluronan synthase protein (e.g., a human collagen protein, a human elastin protein, a human fibronectin protein, a human laminin protein, or a human hyaluronan synthase protein). In some embodiments that may be combined with any of the preceding embodiments, the first collagen protein is a human collagen protein. In some embodiments that may be combined with any of the preceding embodiments, the first collagen protein is selected from a Collagen alpha-l(I) chain polypeptide (COL1-1), Collagen alpha-2(I) chain polypeptide (COL 1-2), a Collagen alpha-1(11) chain polypeptide (COL2), a Collagen alpha-l(III) chain polypeptide (COL3), a Collagen alpha- 1 (IV) chain polypeptide (COL4-1), a Collagen alpha-2(IV) chain polypeptide (COL4-2), a Collagen alpha-3(IV) chain polypeptide (COL4-3), a Collagen alpha-4(IV) chain polypeptide (COL4-4), a Collagen alpha-5(IV) chain polypeptide (COL4-5), a Collagen alpha-6(IV) chain polypeptide (COL4-6), a Collagen alpha-l(V) chain polypeptide (COL5-1), a Collagen alpha-2(V) chain polypeptide (COL5-2), a Collagen alpha-3(V) chain polypeptide (COL5-3), a Collagen alpha-l(VI) chain polypeptide (COL6-1), a Collagen alpha-2(VI) chain polypeptide (COL6-2), a Collagen alpha-3(VI) chain polypeptide (COL6-3), a Collagen alpha-4(VI) chain polypeptide (COL6-4), a Collagen alpha-5(VI) chain polypeptide (COL6-5), a Collagen alpha-6(VI) chain polypeptide (COL6-6), a Collagen alpha- 1 (VIII) chain polypeptide (COL8), a Collagen alpha- 1 (IX) chain polypeptide (COL9-1), a Collagen alpha-2(IX) chain polypeptide (COL9-2), a Collagen alpha-3(IX) chain polypeptide (COL9-3), a Collagen alpha-1(X) chain polypeptide (COL10), a Collagen alpha-l(XI) chain polypeptide (COL11-1), a Collagen alpha-2(XI) chain polypeptide (COL11-2), a Collagen alpha-l(XII) chain polypeptide (COL12), a Collagen alpha-l(XIII) chain polypeptide (COL13), a Collagen alpha-l(XIV) chain polypeptide (COL 14), a Collagen alpha- 1 (XV) chain polypeptide (COL 15), a Collagen alpha- 1 (XVI) chain polypeptide (COL 16), a Collagen alpha- 1 (XVII) chain polypeptide (COL 17), a Collagen alpha- 1 (XVIII) chain polypeptide (COL 18), a Collagen alpha- 1 (XIX) chain polypeptide (COL 19), a Collagen alpha- 1 (XX) chain polypeptide (COL20), a Collagen alpha- 1 (XXI) chain polypeptide (COL21), a Collagen alpha- 1 (XXII)46A97680.DOCXAttorney Docket No.: 10423-2600083 chain polypeptide (COL22), a Collagen alpha- 1 (XXIII) chain polypeptide (COL23), a Collagen alpha- 1 (XXIV) chain polypeptide (COL24), a Collagen alpha- 1 (XXV) chain polypeptide (COL25), a Collagen alpha- 1 (XXVI) chain polypeptide (COL26), a Collagen alpha- 1 (XXVII) chain polypeptide (COL27), and a Collagen alpha- 1 (XXVIII) chain polypeptide (COL28). In some embodiments that may be combined with any of the preceding embodiments, the first collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1, and COL17. In some embodiments that may be combined with any of the preceding embodiments, the first collagen protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments that may be combined with any of the preceding embodiments, the first collagen protein is COL3. In some embodiments that may be combined with any of the preceding embodiments, the first collagen protein is human COL3. In some embodiments that may be combined with any of the preceding embodiments, the first collagen protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 17. In some embodiments that may be combined with any of the preceding embodiments, the first cosmetic protein is not a Collagen alpha-l(VII) chain polypeptide (COL7).

[0012] In some embodiments that may be combined with any of the preceding embodiments, the first cosmetic protein is a human hyaluronan synthase protein. In some embodiments that may be combined with any of the preceding embodiments, the first hyaluronan synthase protein is selected from a hyaluronan synthase 1 protein, a hyaluronan synthase 2 protein, and a hyaluronan synthase 3 protein. In some embodiments that may be combined with any of the preceding embodiments, the first hyaluronan synthase protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 68-70. In some embodiments that may be combined with any of the preceding embodiments, the first hyaluronan synthase protein is a hyaluronan synthase 2 protein. In some embodiments that may be combined with any of the preceding embodiments, the first hyaluronan synthase protein is human hyaluronan synthase 2 protein. In some embodiments that may be combined with any of the preceding embodiments, the first hyaluronan synthase protein comprises a sequence 56A97680.DOCXAttorney Docket No.: 10423-2600083 having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 69. In some embodiments that may be combined with any of the preceding embodiments, the first cosmetic protein is not a Collagen alpha- 1 (VII) chain polypeptide (COL7).

[0013] In some embodiments, the first polypeptide consists essentially of the first cosmetic protein. In some embodiments, the first polypeptide consists of the first cosmetic protein. In some embodiments, the first polypeptide comprises: (a) the first cosmetic protein; (b) a further cosmetic protein; and (c) a linker polypeptide linking (a) to (b). In some embodiments, the further cosmetic protein is selected from a collagen protein, a fibronectin protein, an elastin protein, a lumican protein, a vitronectin protein, a vitronectin receptor protein, a laminin protein, a neuromodulator protein, a fibrillin protein, and a hyaluronan synthase protein. In some embodiments, the further cosmetic protein is a structural extracellular matrix protein (e.g., a collagen protein, an elastin protein, a fibronectin protein, a laminin protein, a fibrillin protein, etc.). In some embodiments, the further cosmetic protein is a collagen protein, an elastin protein, a fibronectin protein, a laminin protein, or a hyaluronan synthase protein (e.g., a human collagen protein, a human elastin protein, a human fibronectin protein, a human laminin protein, or a human hyaluronan synthase protein). In some embodiments, the further collagen protein (e.g., a further human collagen protein) is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6-1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COL10, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, and COL28. In some embodiments, the further collagen protein (e.g., a further human collagen protein) is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1, COL7, and COL 17. In some embodiments, the first cosmetic protein and the further cosmetic protein are different. In some embodiments, the first cosmetic protein is COL1-1 (e.g., human COL1-1) and the further cosmetic protein is COL1-2 (e.g., human COL1-2). In some embodiments, the linker polypeptide is a cleavable linker polypeptide. In some embodiments, the linker polypeptide comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected SEQ ID NOS: 28-31.66A97680.DOCXAttorney Docket No.: 10423-2600083

[0014] In some embodiments that may be combined with any of the preceding embodiments, the first polynucleotide encodes a polycistronic mRNA comprising: (a) a first open reading frame (ORF) encoding the first polypeptide; (b) a second ORF encoding an additional cosmetic protein; and (c) an internal ribosomal entry site (IRES) separating (a) and (b). In some embodiments, the additional cosmetic protein is selected from a collagen protein, a fibronectin protein, an elastin protein, a lumican protein, a vitronectin protein, a vitronectin receptor protein, a laminin protein, a neuromodulator protein, a fibrillin protein, and a hyaluronan synthase protein. In some embodiments, the additional cosmetic protein is a structural extracellular matrix protein (e.g., a collagen protein, an elastin protein, a fibronectin protein, a laminin protein, a fibrillin protein, etc.). In some embodiments, the additional cosmetic protein is a collagen protein, an elastin protein, a fibronectin protein, a laminin protein, or a hyaluronan synthase protein (e.g., a human collagen protein, a human elastin protein, a human fibronectin protein, a human laminin protein, or a human hyaluronan synthase protein). In some embodiments, the additional collagen protein (e.g., an additional human collagen protein) is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6-1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COLIO, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, and COL28. In some embodiments, the additional collagen protein (e.g., an additional human collagen protein) is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1, COL7, and COL17. In some embodiments, the first cosmetic protein and the additional cosmetic protein are different. In some embodiments, the first cosmetic protein is COL1-1 (e.g., human COL1-1) and the additional cosmetic protein is COL1-2 (e.g., human COL1-2). In some embodiments, the nucleic acid sequence encoding the IRES has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NO: 22 or SEQ ID NO: 23.

[0015] In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes virus genome further comprises a second polynucleotide encoding a second cosmetic protein. In some embodiments, the second cosmetic protein is selected from a collagen protein, a fibronectin protein, an elastin protein, a lumican protein, a vitronectin protein, a vitronectin receptor protein, a laminin protein, a neuromodulator protein, a fibrillin protein, and a hyaluronan synthase protein. In some embodiments, the second 76A97680.DOCXAttorney Docket No.: 10423-2600083 cosmetic protein is a structural extracellular matrix protein (e.g., a collagen protein, an elastin protein, a fibronectin protein, a laminin protein, a fibrillin protein, etc.). In some embodiments, the second cosmetic protein is a collagen protein, an elastin protein, a fibronectin protein, a laminin protein, or a hyaluronan synthase protein (e.g., a human collagen protein, a human elastin protein, a human fibronectin protein, a human laminin protein, or a hyaluronan synthase protein). In some embodiments, the second collagen protein (e.g., a second human collagen protein) is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6-1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COLIO, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, and COL28. In some embodiments, the second collagen protein (e.g., a second human collagen protein) is selected from COL1-1, COL 1-2, COL3, COL4-1, COL4-2, COL6-1, COL7, and COL 17. In some embodiments, the first and second cosmetic proteins are different. In some embodiments, the first cosmetic protein is COL1-1 (e.g., human COL1-1) and the second cosmetic protein is COL1-2 (e.g., human COL1-2). In some embodiments, the first cosmetic protein is COL1-1 (e.g., human COL1-1) and the second cosmetic protein is COL3 (e.g., human COL3).

[0016] In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes virus genome further comprises a second polynucleotide encoding a second cosmetic protein. In some embodiments, the second cosmetic protein is selected from a collagen protein, a fibronectin protein, an elastin protein, a lumican protein, a vitronectin protein, a vitronectin receptor protein, a laminin protein, a neuromodulator protein, a fibrillin protein, and a hyaluronan synthase protein. In some embodiments, the second cosmetic protein is a structural extracellular matrix protein (e.g., a collagen protein, an elastin protein, a fibronectin protein, a laminin protein, a fibrillin protein, etc.). In some embodiments, the second cosmetic protein is a collagen protein, an elastin protein, a fibronectin protein, a laminin protein, or a hyaluronan synthase protein (e.g., a human collagen protein, a human elastin protein, a human fibronectin protein, a human laminin protein, or a human hyaluronan synthase protein). In some embodiments, the second cosmetic protein is an elastin protein (e.g., a human elastin protein. In some embodiments, the first and second cosmetic proteins are different. In some embodiments, the first cosmetic protein is COL3 (e.g., human COL3) and the second cosmetic protein is elastin (e.g., human elastin).

[0017] In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes virus genome has reduced cytotoxicity when introduced 86A97680.DOCXAttorney Docket No.: 10423-2600083 into a target cell, as compared to a corresponding wild-type herpes virus genome. In some embodiments, the target cell is a cell of the epidermis and / or dermis. In some embodiments, the target cell is a human cell. In some embodiments, the target cell is a fibroblast or a keratinocyte.

[0018] Other aspects of the present disclosure relate to a herpes virus comprising any of the recombinant herpes virus genomes described herein. In some embodiments, the herpes virus is replication competent. In some embodiments, the herpes virus is replication defective. In some embodiments, the herpes virus is attenuated. In some embodiments that may be combined with any of the preceding embodiments, the herpes virus has reduced cytotoxicity as compared to a corresponding wild-type herpes virus. In some embodiments that may be combined with any of the preceding embodiments, the herpes virus is selected from 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. In some embodiments that may be combined with any of the preceding embodiments, the herpes virus is a herpes simplex virus. In some embodiments, the herpes simplex virus is a herpes simplex virus type 1 (HSV-1), a herpes simplex virus type 2 (HSV-2), or any derivatives thereof. In some embodiments, the herpes simplex virus is a herpes simplex virus type 1 (HSV-1).

[0019] Other aspects of the present disclosure relate to a composition comprising: (a) any of the recombinant herpes virus genomes described herein and / or any of the herpes viruses described herein; and (b) an excipient. In some embodiments, the composition is sterile. In some embodiments that may be combined with any of the preceding embodiments, the composition is suitable for topical, transdermal, subcutaneous, intradermal, oral, intranasal, intratracheal, sublingual, buccal, rectal, vaginal, inhaled, intravenous, intraarterial, intramuscular, intracardiac, intraosseous, intraperitoneal, transmucosal, intravitreal, subretinal, intraarticular, peri-articular, local, or epicutaneous administration. In some embodiments that may be combined with any of the preceding embodiments, the composition is suitable for intradermal administration. In some embodiments that may be combined with any of the preceding embodiments, the composition is suitable for superficial injection. In some embodiments that may be combined with any of the preceding embodiments, the composition is administered by micro-depot injection. In some embodiments that may be combined with any of the preceding embodiments, the composition is a cosmetic composition. In some embodiments that may be combined with any of the preceding embodiments, the composition is a skin care product.96A97680.DOCXAttorney Docket No.: 10423-2600083

[0020] Other aspects of the present disclosure relate to the use of any of the recombinant herpes virus genomes described herein and / or any of the herpes viruses described herein as a medicament (e.g., for an aesthetic indication).

[0021] Other aspects of the present disclosure relate to the use of any of the recombinant herpes virus genomes described herein and / or any of the herpes viruses described herein as a therapy (e.g., as an aesthetic or cosmetic therapy).

[0022] Other aspects of the present disclosure relate to the use of any of the recombinant herpes virus genomes described herein and / or any of the herpes viruses described herein in the manufacture of a medicament useful for treating one or more signs or symptoms of dermatological aging.

[0023] Other aspects of the present disclosure relate to the use of any of the recombinant herpes virus genomes described herein and / or any of the herpes viruses described herein in the manufacture of a medicament useful for treating a subject’s decollete.

[0024] Other aspects of the present disclosure relate to a method of enhancing, increasing, augmenting, and / or supplementing the levels of one or more dermal extracellular matrix proteins in a subject, the method comprising administering to the subject an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein.

[0025] Other aspects of the present disclosure relate to a method of enhancing, increasing, augmenting, and / or supplementing the levels of one or more dermal extracellular matrix proteins in a subject’s decollete, the method comprising administering to the subject’s decollete an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein.

[0026] Other aspects of the present disclosure relate to a method of enhancing, increasing, augmenting, and / or supplementing the levels of one or more collagen proteins in a subject, the method comprising administering to the subject an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein. In some embodiments, the one or more collagen proteins are collagen 3. In some embodiments, the levels of endogenous collagen 3 are reduced as a result of chronological or photo-aging.

[0027] Other aspects of the present disclosure relate to a method of enhancing, increasing, augmenting, and / or supplementing the levels of one or more collagen proteins, one or more elastin proteins, and / or one or more hyaluronan synthase proteins in a subject, the method comprising administering to the subject an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein. In some embodiments, the106A97680.DOCXAttorney Docket No.: 10423-2600083 one or more collagen proteins is collagen 3. In some embodiments, the one or more hyaluronan synthase proteins is hyaluronan synthase 2.

[0028] Other aspects of the present disclosure relate to a method of enhancing, increasing, augmenting, and / or supplementing the soft tissue of a subject, the method comprising administering to the subject an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein. In some embodiments, the composition is injected into the soft tissue of the subject.

[0029] Other aspects of the present disclosure relate to a method of improving skin condition, quality, and / or appearance in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein. In some embodiments, the composition is administered to one or more sites of sun damage or other UV exposure, rough texture, skin sagging, wrinkles, or any combinations thereof.

[0030] Other aspects of the present disclosure relate to a method of improving the condition, quality, and / or appearance of a subject’s decollete, the method comprising administering to the subject an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein. In some embodiments, the composition is administered to one or more sites of sun damage or other UV exposure, rough texture, skin sagging, wrinkles, or any combinations thereof.

[0031] Other aspects of the present disclosure relate to a method of reducing the appearance of one or more superficial depressions in the skin of a subject in need thereof, the method comprising administering to the subject an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein. In some embodiments, the one or more superficial depressions in the skin are selected from the group consisting of nasolabial folds, crows’ feet, frown lines, worry lines, scars, glabellar lines, brow ptosis, tear troughs, nasojugal lines, bunny lines, cheek / mid-face ptosis, marionette lines, poppy dimpling, smile lines, laugh lines, chin creases, neck lines, platysma bands, and any combinations thereof.

[0032] Other aspects of the present disclosure relate to a method of reducing the appearance of one or more superficial depressions of a subject’s decollete, the method comprising administering to the subject’s decollete an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein. In some embodiments, the one or more superficial depressions in the skin are selected from the group consisting of scars, poikiloderma of Civatte, hyperpigmentation, upper chest lines, chest wrinkles, neck lines, neck wrinkles, platysma bands, and any combinations thereof.116A97680.DOCXAttorney Docket No.: 10423-2600083

[0033] Other aspects of the present disclosure relate to a method of increasing and / or improving at least one of texture, smoothness, elasticity, pigmentation, thinness, hydration, or tension of the skin of a subject in need thereof, the method comprising administering to the subject an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein.

[0034] Other aspects of the present disclosure relate to a method of increasing and / or improving at least one of texture, smoothness, elasticity, pigmentation, thinness, hydration, or tension of a subject’s decollete, the method comprising administering to the subject’s decollete an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein.

[0035] In some embodiments that may be combined with any of the preceding embodiments, the skin of the subject (e.g., the decollete of the subject) is aging skin. In some embodiments that may be combined with any of the preceding embodiments, the skin of the subject (e.g., the decollete of the subject) has been damaged due to exposure to ultraviolet light. In some embodiments that may be combined with any of the preceding embodiments, the skin of the subject (e.g., the decollete of the subject) is wrinkled.

[0036] Other aspects of the present disclosure relate to a method of diminishing one or more dermatological signs of aging in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein. In some embodiments, the diminishing of one or more dermatological signs of aging is indicated by the: (a) treatment, reduction, and / or prevention of fine lines and / or wrinkles; (b) reduction of skin pore size; (c) improvement in skin thickness, plumpness, and / or tautness; (d) improvement in skin smoothness, suppleness, and / or softness; (e) improvement in skin tone, radiance, and / or clarity; (f) improvement in procollagen and / or collagen production; (g) improvement in skin texture and or promotion of retexturization; (h) improvement in appearance of skin contours; (i) restoration of skin luster and / or brightness; (j) improvement of skin appearance decreased by aging and / or menopause; (k) improvement in skin moisturization; (1) increase in skin elasticity and / or resiliency; (m) treatment, reduction, and / or prevention or skin sagging; (n) improvement in skin firmness; (o) reduction of pigment spots, mottled skin, and / or scars (such as acne scars); (p) improvement of optical properties of skin by light diffraction or reflection; (q) improvement in skin pigmentation; (r) improvement in skin thinness; (s) improvement in skin hydration; or (t) any combinations thereof.126A97680.DOCXAttorney Docket No.: 10423-2600083

[0037] Other aspects of the present disclosure relate to a method of diminishing one or more dermatological signs of aging of a subject’s decollete, the method comprising administering to the subject’s decollete an effective amount of any of the herpes viruses described herein and / or any of the compositions described herein. In some embodiments, the diminishing of one or more dermatological signs of aging of the subject’s decollete is indicated by the: (a) treatment, reduction, and / or prevention of fine lines and / or wrinkles; (b) reduction of skin pore size; (c) improvement in skin thickness, plumpness, and / or tautness; (d) improvement in skin smoothness, suppleness, and / or softness; (e) improvement in skin tone, radiance, and / or clarity; (f) improvement in procollagen and / or collagen production; (g) improvement in skin texture and or promotion of retexturization; (h) improvement in appearance of skin contours; (i) restoration of skin luster and / or brightness; (j) improvement of skin appearance decreased by aging and / or menopause; (k) improvement in skin moisturization; (1) increase in skin elasticity and / or resiliency; (m) treatment, reduction, and / or prevention or skin sagging; (n) improvement in skin firmness; (o) reduction of pigment spots, mottled skin, and / or scars (such as acne scars); (p) improvement of optical properties of skin by light diffraction or reflection; (q) improvement in skin pigmentation; (r) improvement in skin thinness; (s) improvement in skin hydration; or (t) any combinations thereof.

[0038] In some embodiments that may be combined with any of the preceding embodiments, the subject is a human. In some embodiments that may be combined with any of the preceding embodiments, the herpes virus or composition is administered topically, transdermally, subcutaneously, epicutaneously, intradermally, orally, sublingually, buccally, rectally, vaginally, intravenously, intraarterially, intramuscularly, intraosseously, intracardially, intraperitoneally, transmucosally, intravitreally, subretinally, intraarticularly, peri-articularly, locally, or via inhalation to the subject. In some embodiments that may be combined with any of the preceding embodiments, the herpes virus or composition is administered intradermally to the subject. In some embodiments that may be combined with any of the preceding embodiments, the herpes virus or composition is administered by superficial injection. In some embodiments that may be combined with any of the preceding embodiments, the herpes virus or composition is administered by micro-depot injection. In some embodiments that may be combined with any of the preceding embodiments, the herpes virus or composition is administered intradermally to the subject. In some embodiments that may be combined with any of the preceding embodiments, the herpes virus or composition is administered by injection. In some embodiments that may be combined with any of the136A97680.DOCXAttorney Docket No.: 10423-2600083 preceding embodiments, the herpes virus or composition is administered by superficial injection.

[0039] In some embodiments that may be combined with any of the preceding embodiments, the method further comprises applying a grid to the subject’s decollete to mark one or more injection sites. In some embodiments that may be combined with any of the preceding embodiments, the one or more injection sites are spaced about 0.5 cm, about 1.0 cm, about 1.5 cm, about 2.0 cm, about 2.5 cm, about 3.0 cm, about 3.5 cm, about 4.0 cm, about 4.5 cm, or about 5.0 cm apart from each other. In some embodiments that may be combined with any of the preceding embodiments, administering the composition comprises one or more injections at each of the one or more injection sites. In some embodiments that may be combined with any of the preceding embodiments, the one or more injections may each deliver about 0.01 mL, 0.02 mL, 0.03 mL, 0.04 mL, 0.05 mL, 0.06 mL, 0.07 mL, 0.08 mL, 0.09 mL, 0.10 mL, 0.11 mL, 0.12 mL, 0.13 mL, 0.14 mL, 0.15 mL, 0.16 mL, 0.17 mL, 0.18 mL, 0.19 mL, 0.20 mL, 0.21 mL, 0.22 mL, 0.23 mL, 0.24 mL, 0.25 mL, 0.26 mL, 0.27 mL, 0.28 mL, 0.29 mL, 0.30 mL, 0.31 mL, 0.32 mL, 0.33 mL, 0.34 mL, 0.35 mL, 0.36 mL, 0.37 mL, 0.38 mL, 0.39 mL, 0.40 mL, 0.41 mL, 0.42 mL, 0.43 mL, 0.44 mL, 0.45 mL, 0.46 mL, 0.47 mL, 0.48 mL, 0.49 mL, 0.50 mL, 0.51 mL, 0.52 mL, 0.53 mL, 0.54 mL, 0.55 mL, 0.56 mL, 0.57 mL, 0.58 mL, 0.59 mL, 0.60 mL, 0.61 mL, 0.62 mL, 0.63 mL, 0.64 mL, 0.65 mL, 0.66 mL, 0.67 mL, 0.68 mL, 0.69 mL, 0.70 mL, 0.71 mL, 0.72 mL, 0.73 mL, 0.74 mL, 0.75 mL, 0.76 mL, 0.77 mL, 0.78 mL, 0.79 mL, 0.80 mL, 0.81 mL, 0.82 mL, 0.83 mL, 0.84 mL, 0.85 mL, 0.86 mL, 0.87 mL, 0.88 mL, 0.89 mL, 0.90 mL, 0.91 mL, 0.92 mL, 0.93 mL, 0.94 mL, 0.95 mL, 0.96 mL, 0.97 mL, 0.98 mL, 0.99 mL, or 1.00 mL of the recombinant herpes virus genomes, herpes viruses, compositions and / or formulations described herein. In some embodiments that may be combined with any of the preceding embodiments, administering the composition occurs at least once per day for up to 60 days. In some embodiments that may be combined with any of the preceding embodiments, administering the composition comprises administering the herpes virus or composition at a concentration in a range from about IxlO4PFU / mL to about IxlO12PFU / mL. In some embodiments that may be combined with any of the preceding embodiments, the method further comprise administering to the subject’s decollete an agent selected from the group consisting of an anesthetic agent, an anti-microbial agent, a vasoconstrictor, an anti-thrombotic agent, an anti-coagulation agent, a dispersion agent, an anti-dispersion agent, a penetration enhancer, a steroid, a tranquilizer, a muscle relaxant, an anti-diarrhea agent, or any combination thereof.146A97680.DOCXAttorney Docket No.: 10423-2600083

[0040] Other aspects of the present disclosure relate to a composition comprising: a herpes simplex virus (HSV) comprising a recombinant nucleic acid, wherein the recombinant nucleic acid comprises a first polynucleotide encoding a first polypeptide comprising a first human collagen protein, and an excipient. In some embodiments, the recombinant nucleic acid comprises two or more copies of the first polynucleotide. In some embodiments that may be combined with any of the preceding embodiments, the HSV is replication-defective. In some embodiments that may be combined with any of the preceding embodiments, the HSV is replication-competent. In some embodiments that may be combined with any of the preceding embodiments, the HSV is a herpes simplex virus type 1, a herpes simplex virus type 2, or any derivatives thereof.

[0041] In some embodiments, the recombinant nucleic acid is a herpes simplex virus amplicon. In some embodiments, the herpes simplex virus amplicon is an HSV-1 amplicon or an HSV-1 hybrid amplicon. In some embodiments, the HSV-1 hybrid amplicon is an HSV / AAV hybrid amplicon, an HSVZEBV hybrid amplicon, and HSV / EBV / RV hybrid amplicon, or an HSV / Sleeping Beauty hybrid amplicon.

[0042] In some embodiments, the recombinant nucleic acid is a recombinant herpes simplex virus genome. In some embodiments, the recombinant herpes simplex virus genome is a recombinant HSV-1 genome, a recombinant HSV-2 genome, or any derivatives thereof. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in a herpes simplex virus gene. In some embodiments, the herpes simplex virus gene is selected from the group consisting of Infected Cell Protein (ICP) 0, ICP4, ICP22, ICP27, ICP47, thymidine kinase (tk), Long Unique Region (UL) 41, and UL55. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in one or both copies of the ICP4 gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP22 gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the UL41 gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP0 gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP27 gene. In some156A97680.DOCXAttorney Docket No.: 10423-2600083 embodiments that may be combined with any of the preceding embodiments, the inactivating mutation is a deletion of the coding sequence of the gene(s).

[0043] In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within a viral gene locus. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within one or both copies of the ICP4 viral gene loci. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within the ICP22 viral gene locus. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within the UL41 viral gene locus. In some embodiments that may be combined with any of the preceding embodiments, the HSV has reduced cytotoxicity as compared to a wild-type herpes simplex virus.

[0044] In some embodiments that may be combined with any of the preceding embodiments, the first human collagen protein is selected from Collagen alpha- 1(1) chain polypeptide (COL1-1), Collagen alpha-2(I) chain polypeptide (COL 1-2), a Collagen alpha-1(11) chain polypeptide (COL2), a Collagen alpha-l(III) chain polypeptide (COL3), a Collagen alpha- 1 (IV) chain polypeptide (COL4-1), a Collagen alpha-2(IV) chain polypeptide (COL4-2), a Collagen alpha-3(IV) chain polypeptide (COL4-3), a Collagen alpha-4(IV) chain polypeptide (COL4-4), a Collagen alpha-5(IV) chain polypeptide (COL4-5), a Collagen alpha-6(IV) chain polypeptide (COL4-6), a Collagen alpha-l(V) chain polypeptide (COL5-1), a Collagen alpha-2(V) chain polypeptide (COL5-2), a Collagen alpha-3(V) chain polypeptide (COL5-3), a Collagen alpha-l(VI) chain polypeptide (COL6-1), a Collagen alpha-2(VI) chain polypeptide (COL6-2), a Collagen alpha-3(VI) chain polypeptide (COL6-3), a Collagen alpha-4(VI) chain polypeptide (COL6-4), a Collagen alpha-5(VI) chain polypeptide (COL6-5), a Collagen alpha-6(VI) chain polypeptide (COL6-6), a Collagen alpha- 1 (VII) chain polypeptide (COL7), a Collagen alpha- 1 (VIII) chain polypeptide (COL8), a Collagen alpha- 1 (IX) chain polypeptide (COL9-1), a Collagen alpha-2(IX) chain polypeptide (COL9-2), a Collagen alpha-3(IX) chain polypeptide (COL9-3), a Collagen alpha-l(X) chain polypeptide (COLIO), a Collagen alpha- 1 (XI) chain polypeptide (COL11-1), a Collagen alpha-2(XI) chain polypeptide (COL11-2), a Collagen alpha-l(XII) chain polypeptide (COL12), a Collagen alpha-l(XIII) chain polypeptide (COL13), a Collagen alpha-l(XIV) chain polypeptide (COL14), a Collagen alpha- 1 (XV) chain polypeptide (COL 15), a Collagen alpha- 1 (XVI) chain polypeptide (COL 16), a Collagen alpha- 1 (XVII) chain polypeptide (COL 17), a Collagen alpha- 1 (XVIII)166A97680.DOCXAttorney Docket No.: 10423-2600083 chain polypeptide (COL 18), a Collagen alpha- 1 (XIX) chain polypeptide (COL 19), a Collagen alpha- 1 (XX) chain polypeptide (COL20), a Collagen alpha- 1 (XXI) chain polypeptide (COL21), a Collagen alpha- 1 (XXII) chain polypeptide (COL22), a Collagen alpha- 1 (XXIII) chain polypeptide (COL23), a Collagen alpha- 1 (XXIV) chain polypeptide (COL24), a Collagen alpha- 1 (XXV) chain polypeptide (COL25), a Collagen alpha- 1 (XXVI) chain polypeptide (COL26), a Collagen alpha- 1 (XXVII) chain polypeptide (COL27), and a Collagen alpha- 1 (XXVIII) chain polypeptide (COL28). In some embodiments that may be combined with any of the preceding embodiments, the first human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL6-1, COL7, and COL17. In some embodiments that may be combined with any of the preceding embodiments, the nucleic acid sequence encoding the first human collagen protein has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NOS: 1-14. In some embodiments that may be combined with any of the preceding embodiments, the first human collagen protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments that may be combined with any of the preceding embodiments, the first human collagen protein is not COL7.

[0045] In some embodiments that may be combined with any of the preceding embodiments, the first polypeptide comprises: (a) the first human collagen protein; (b) a further human collagen protein; and (c) a linker polypeptide linking (a) to (b). In some embodiments, the linker polypeptide is a cleavable linker polypeptide. In some embodiments, the linker polypeptide comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 28-31. In some embodiments, the further human collagen protein is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6-1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COL10, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, and COL28. In some embodiments, the further human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL6-1, COL7, and COL17. In some embodiments, the nucleic acid sequence encoding the further human collagen protein has at 176A97680.DOCXAttorney Docket No.: 10423-2600083 least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NOS: 1-14. In some embodiments, the further human collagen protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments, the first human collagen protein and the further human collagen protein are different.

[0046] In some embodiments that may be combined with any of the preceding embodiments, the first polynucleotide encodes a polycistronic mRNA comprising: (a) a first open reading frame (ORF) encoding the first polypeptide; (b) a second ORF encoding an additional human collagen protein; and (c) an internal ribosomal entry site (IRES) separating (a) and (b). In some embodiments, the nucleic acid sequence encoding the IRES has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments, the additional human collagen protein is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6-1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COL10, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, and COL28. In some embodiments, the additional human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL6-1, COL7, and COL17. In some embodiments, the nucleic acid sequence encoding the additional human collagen protein has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NOS: 1-14. In some embodiments, the additional human collagen protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments, the first human collagen protein and the additional human collagen protein are different.

[0047] In some embodiments that may be combined with any of the preceding embodiments, the recombinant nucleic acid further comprises a second polynucleotide 186A97680.DOCXAttorney Docket No.: 10423-2600083 encoding a second human collagen protein. In some embodiments, the recombinant nucleic acid comprises two or more copies of the second polynucleotide. In some embodiments, the second human collagen protein is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6-1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COLIO, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, and COL28. In some embodiments, the second human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL6-1, COL7, and COL17. In some embodiments, the nucleic acid sequence encoding the second human collagen protein has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NOS: 1-14. In some embodiments, the second human collagen protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments, the first and second human collagen proteins are different.

[0048] In some embodiments that may be combined with any of the preceding embodiments, the recombinant nucleic acid further comprises a second polynucleotide encoding an elastin protein, in some embodiments, the elastin protein is a human elastin protein. In some embodiments, the recombinant nucleic acid comprises two or more copies of the second polynucleotide.

[0049] In some embodiments that may be combined with any of the preceding embodiments, the recombinant nucleic acid is a recombinant herpes simplex virus genome, and wherein the recombinant herpes simplex virus genome comprises the second polynucleotide within a viral gene locus. In some embodiments, the recombinant herpes simplex virus genome comprises the second polynucleotide within one or both copies of the ICP4 viral gene loci. In some embodiments, the recombinant herpes simplex virus genome comprises the second polynucleotide within the ICP22 viral gene locus. In some embodiments, the recombinant herpes simplex virus genome comprises the second polynucleotide within the UL41 viral gene locus. In some embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within one or both copies of the ICP4 viral gene loci and the second polynucleotide within the ICP22 viral gene locus. In some embodiments, the recombinant196A97680.DOCXAttorney Docket No.: 10423-2600083 herpes simplex virus genome comprises the first polynucleotide within one or both copies of the ICP4 viral gene loci and the second polynucleotide within the UL41 viral gene locus.

[0050] In some embodiments that may be combined with any of the preceding embodiments, the excipient is adapted for cutaneous (systemic or topical), transdermal, subcutaneous, and / or intradermal administration. In some embodiments that may be combined with any of the preceding embodiments, the excipient comprises a hydroxypropyl methylcellulose gel. In some embodiments that may be combined with any of the preceding embodiments, the excipient is adapted for intradermal administration. In some embodiments that may be combined with any of the preceding embodiments, the excipient comprises a phosphate buffer. In some embodiments that may be combined with any of the preceding embodiments, the excipient comprises glycerol. In some embodiments that may be combined with any of the preceding embodiments, the excipient comprises a lipid carrier. In some embodiments that may be combined with any of the preceding embodiments, the excipient comprises a nanoparticle carrier.

[0051] In some embodiments that may be combined with any of the preceding embodiments, the composition is a cosmetic composition. In some embodiments, the cosmetic composition is a skin care product.

[0052] Other aspects of the present disclosure relate to a kit comprising any of the compositions described herein and instructions for administering the composition.

[0053] Other aspects of the present disclosure relate to a method of enhancing, increasing, augmenting, and / or supplementing the levels of one or more human collagen and / or elastin proteins in a subject, the method comprising administering to the subject an effective amount of any of the compositions described herein.

[0054] Other aspects of the present disclosure relate to a method of enhancing, increasing, augmenting, and / or supplementing the levels of one or more human collagen and / or elastin proteins in a subject’s decollete, the method comprising administering to the subject’s decollete an effective amount of any of the compositions described herein.

[0055] Other aspects of the present disclosure relate to a method of enhancing, increasing, augmenting, and / or supplementing soft tissue of a subject, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, the composition is injected into a soft tissue of the subject.

[0056] Other aspects of the present disclosure relate to a method of enhancing, increasing, augmenting, and / or supplementing soft tissue of a subject’s decollete, the method comprising administering to the subject’s decollete an effective amount of any of the compositions 206A97680.DOCXAttorney Docket No.: 10423-2600083 described herein. In some embodiments, the composition is injected into a soft tissue of the subject’s decollete.

[0057] Other aspects of the present disclosure relate to a method of improving skin quality, condition and / or appearance in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, the condition is selected from sun damage, aging, UV exposure, rough texture, skin sagging, wrinkles, and any combinations thereof.

[0058] Other aspects of the present disclosure relate to a method of improving skin quality, condition and / or appearance in a subject’s decollete in need thereof, the method comprising administering to the subject’s decollete an effective amount of any of the compositions described herein. In some embodiments, the condition is selected from sun damage, aging, UV exposure, rough texture, skin sagging, wrinkles, and any combinations thereof.

[0059] Other aspects of the present disclosure relate to a method of reducing the appearance of one or more superficial depressions in the skin of a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, administration of the composition reduces the appearance of the one or more superficial depressions in the skin of the subject for at least about three months, at least about six months, at least about nine months, or at least about 12 months. In some embodiments, the appearance of the one or more superficial depressions in the skin of the subject is reduced after administration of the composition, as compared to the appearance of the one or more superficial depression in the skin of the subject prior to administration of the composition.

[0060] Other aspects of the present disclosure relate to a method of reducing the appearance of one or more superficial depressions in the skin of a subject’s decollete in need thereof, the method comprising administering to the subject’s decollete an effective amount of any of the compositions described herein. In some embodiments, administration of the composition reduces the appearance of the one or more superficial depressions in the skin of the subject for at least about three months, at least about six months, at least about nine months, or at least about 12 months. In some embodiments, the appearance of the one or more superficial depressions in the skin of the subject’s decollete is reduced after administration of the composition, as compared to the appearance of the one or more superficial depression in the skin of the subject’s decollete prior to administration of the composition.

[0061] Other aspects of the present disclosure relate to a method of increasing and / or improving at least one of texture, smoothness, elasticity, pigmentation, thinness, hydration, or 216A97680.DOCXAttorney Docket No.: 10423-2600083 tension of the skin of a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, the skin of the subject maintains at least one of an increased and / or improved texture, smoothness, elasticity, pigmentation, thinness, hydration, or tension for at least about three months, at least about six months, at least about nine months, or at least about 12 months after administration of the composition. In some embodiments, at least one of texture, smoothness, elasticity, pigmentation, thinness, hydration, or tension of the skin of the subject is increased and / or improved after administration of the composition, as compared to the texture, smoothness, elasticity, pigmentation, thinness, hydration, or tension of the skin of the subject prior to administration of the composition.

[0062] Other aspects of the present disclosure relate to a method of increasing and / or improving at least one of texture, smoothness, elasticity, pigmentation, thinness, hydration, or tension of the skin of a subject’s decollete in need thereof, the method comprising administering to the subject’s decollete an effective amount of any of the compositions described herein. In some embodiments, the skin of the subject’s decollete maintains at least one of an increased and / or improved texture, smoothness, elasticity, pigmentation, thinness, hydration, or tension for at least about three months, at least about six months, at least about nine months, or at least about 12 months after administration of the composition. In some embodiments, at least one of texture, smoothness, elasticity, pigmentation, thinness, hydration, or tension of the skin of the subject’s decollete is increased and / or improved after administration of the composition, as compared to the texture, smoothness, elasticity, pigmentation, thinness, hydration, or tension of the skin of the subject’s decollete prior to administration of the composition.

[0063] In some embodiments that may be combined with any of the preceding embodiments, the skin of the subject is aging skin. In some embodiments that may be combined with any of the preceding embodiments, the skin of the subject has been damaged due to exposure to ultraviolet light. In some embodiments that may be combined with any of the preceding embodiments, the skin of the subject is wrinkled.

[0064] In some embodiments that may be combined with any of the preceding embodiments, the skin of the subject’s decollete is aging skin. In some embodiments that may be combined with any of the preceding embodiments, the skin of the subject’s decollete has been damaged due to exposure to ultraviolet light. In some embodiments that may be combined with any of the preceding embodiments, the skin of the subject’s decollete is wrinkled.226A97680.DOCXAttorney Docket No.: 10423-2600083

[0065] Other aspects of the present disclosure relate to a method of diminishing one or more dermatological signs of aging in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, the diminishing of one or more dermatological signs of aging is selected from: (a) treatment, reduction, and / or prevention of fine lines and / or wrinkles; (b) reduction of skin pore size; (c) improvement in skin thickness, plumpness, and / or tautness; (d) improvement in skin smoothness, suppleness, and / or softness; (e) improvement in skin tone, radiance, and / or clarity; (f) improvement in procollagen and / or collagen production; (g) improvement in skin texture and or promotion of retexturization; (h) improvement in appearance of skin contours; (i) restoration of skin luster and / or brightness; (j) improvement of skin appearance decreased by aging and / or menopause; (k) improvement in skin moisturization; (1) increase in skin elasticity and / or resiliency; (m) treatment, reduction, and / or prevention or skin sagging; (n) improvement in skin firmness; (o) reduction of pigment spots, mottled skin, and / or acne scars; (p) improvement of optical properties of skin by light diffraction or reflection; (q) improvement in skin pigmentation; (r) improvement in skin thinness; (s) improvement in skin hydration; and (t) any combinations thereof. In some embodiments, the one or more dermatological signs of aging in the subject is diminished after administration of the composition, as compared to the one or more dermatological signs of aging in the subject prior to administration of the composition.

[0066] Other aspects of the present disclosure relate to a method of diminishing one or more dermatological signs of aging in a subject’s decollete in need thereof, the method comprising administering to the subject’s decollete an effective amount of any of the compositions described herein. In some embodiments, the diminishing of one or more dermatological signs of aging is selected from: (a) treatment, reduction, and / or prevention of fine lines and / or wrinkles; (b) reduction of skin pore size; (c) improvement in skin thickness, plumpness, and / or tautness; (d) improvement in skin smoothness, suppleness, and / or softness; (e) improvement in skin tone, radiance, and / or clarity; (f) improvement in procollagen and / or collagen production; (g) improvement in skin texture and or promotion of retexturization; (h) improvement in appearance of skin contours; (i) restoration of skin luster and / or brightness; (j) improvement of skin appearance decreased by aging and / or menopause; (k) improvement in skin moisturization; (1) increase in skin elasticity and / or resiliency; (m) treatment, reduction, and / or prevention or skin sagging; (n) improvement in skin firmness; (o) reduction of pigment spots, mottled skin, and / or acne scars; (p) improvement of optical properties of skin by light diffraction or reflection; (q) improvement in skin pigmentation; (r) improvement in skin 236A97680.DOCXAttorney Docket No.: 10423-2600083 thinness; (s) improvement in skin hydration; and (t) any combinations thereof. In some embodiments, the one or more dermatological signs of aging in the subject is diminished after administration of the composition, as compared to the one or more dermatological signs of aging in the subject prior to administration of the composition.

[0067] In some embodiments that may be combined with any of the preceding embodiments, the subject is a human. In some embodiments that may be combined with any of the preceding embodiments, the composition is administered cutaneously (systemically or topically), transdermally, subcutaneously, or intradermally to the subject. In some embodiments, the composition is administered by superficial injection. In some embodiments, the composition is administered by micro-depot injection. In some embodiments, the composition is administered intradermally to the subject. In some embodiments, the composition is administered once to the subject. In some embodiments, the composition is administered at least twice to the subject. In some embodiments, at least about 15, at least about 30, at least about 60, at least about 90, or at least about 120 days passes between administrations. In some embodiments that may be combined with any of the preceding embodiments, the composition is administered to one or more affected and / or unaffected areas of the subject. In some embodiments that may be combined with any of the preceding embodiments, the skin of the is abraded prior to administration.

[0068] Other aspects of the present disclosure relate to a recombinant nucleic acid comprising a first polynucleotide encoding a first polypeptide comprising a first human collagen protein, wherein the recombinant nucleic acid is a recombinant herpes simplex virus genome. In some embodiments, the recombinant nucleic acid comprises two or more copies of the first polynucleotide. In some embodiments, the recombinant herpes simplex virus genome is a recombinant HSV-1 genome, a recombinant HSV-2 genome, or any derivatives thereof.

[0069] In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in a herpes simplex virus gene. In some embodiments, the herpes simplex virus gene is selected from the group consisting of Infected Cell Protein (ICP) 0, ICP4, ICP22, ICP27, ICP47, thymidine kinase (tk), Long Unique Region (UL) 41, and UL55. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in one or both copies of the ICP4 gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP22 gene. In some embodiments that may be combined with any of the preceding embodiments,246A97680.DOCXAttorney Docket No.: 10423-2600083 the recombinant herpes simplex virus genome comprises an inactivation mutation in the UL41 gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICPO gene. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP27 gene. In some embodiments that may be combined with any of the preceding embodiments, the inactivating mutation is a deletion of the coding sequence of the gene(s).

[0070] In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within a viral gene locus. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within one or both copies of the ICP4 viral gene loci. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within the ICP22 viral gene locus. In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within the UL41 viral gene locus. In some embodiments that may be combined with any of the preceding embodiments, the HSV has reduced cytotoxicity as compared to a wild-type herpes simplex virus.

[0071] In some embodiments that may be combined with any of the preceding embodiments, the first human collagen protein is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6-1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COL10, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, and COL2. In some embodiments that may be combined with any of the preceding embodiments, the first human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL6-1, COL7, and COL 17. In some embodiments that may be combined with any of the preceding embodiments, the nucleic acid sequence encoding the first human collagen protein has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NOS: 1-14. In some embodiments that may be combined with any of the preceding embodiments, the first human collagen protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%256A97680.DOCXAttorney Docket No.: 10423-2600083 sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments that may be combined with any of the preceding embodiments, the first human collagen protein is not COL7.

[0072] In some embodiments that may be combined with any of the preceding embodiments, the first polypeptide comprises: (a) the first human collagen protein; (b) a further human collagen protein; and (c) a linker polypeptide linking (a) to (b). In some embodiments, the linker polypeptide is a cleavable linker polypeptide. In some embodiments, the linker polypeptide comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 28-31. In some embodiments, the further human collagen protein is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6-1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COL10, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, and COL28. In some embodiments, the further human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL6-1, COL7, and COL17. In some embodiments, the nucleic acid sequence encoding the further human collagen protein has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NOS: 1-14. In some embodiments, the further human collagen protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments, the first human collagen protein and the further human collagen protein are different.

[0073] In some embodiments that may be combined with any of the preceding embodiments, the first polynucleotide encodes a polycistronic mRNA comprising: (a) a first open reading frame (ORF) encoding the first polypeptide; (b) a second ORF encoding an additional human collagen protein; and (c) an internal ribosomal entry site (IRES) separating (a) and (b). In some embodiments, the nucleic acid sequence encoding the IRES has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments,266A97680.DOCXAttorney Docket No.: 10423-2600083 the additional human collagen protein is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6- 1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COLIO, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, and COL28. In some embodiments, the additional human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL6-1, COL7, and COL17. In some embodiments, the nucleic acid sequence encoding the additional human collagen protein has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NOS: 1-14. In some embodiments, the additional human collagen protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments, the first human collagen protein and the additional human collagen protein are different.

[0074] In some embodiments that may be combined with any of the preceding embodiments, the recombinant nucleic acid further comprises a second polynucleotide encoding a second human collagen protein. In some embodiments, the recombinant nucleic acid comprises two or more copies of the second polynucleotide. In some embodiments, the second human collagen protein is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6-1, COL6- 2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COL10, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, and COL28. In some embodiments, the second human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL6-1, COL7, and COL17. In some embodiments, the nucleic acid sequence encoding the second human collagen protein has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NOS: 1-14. In some embodiments, the second human collagen protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%276A97680.DOCXAttorney Docket No.: 10423-2600083 sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments, the first and second human collagen proteins are different.

[0075] In some embodiments that may be combined with any of the preceding embodiments, the recombinant nucleic acid further comprises a second polynucleotide encoding a second polypeptide comprising an elastin protein. In some embodiments, the recombinant nucleic acid comprises two or more copies of the second polynucleotide.

[0076] In some embodiments that may be combined with any of the preceding embodiments, the recombinant herpes simplex virus genome comprises the second polynucleotide within a viral gene locus. In some embodiments, the recombinant herpes simplex virus genome comprises the second polynucleotide within one or both copies of the ICP4 viral gene loci. In some embodiments, the recombinant herpes simplex virus genome comprises the second polynucleotide within the ICP22 viral gene locus. In some embodiments, the recombinant herpes simplex virus genome comprises the second polynucleotide within the UL41 viral gene locus. In some embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within one or both copies of the ICP4 viral gene loci and the second polynucleotide within the ICP22 viral gene locus. In some embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within one or both copies of the ICP4 viral gene loci and the second polynucleotide within the UL41 viral gene locus.

[0077] Other aspects of the present disclosure relate to a host cell comprising any of the recombinant nucleic acids described herein. In some embodiments, the host cell is a eukaryotic cell. In some embodiments, the host cell is a mammalian cell. In some embodiments, the host cell is a human cell or a non-human primate cell. In some embodiments, the host cell is a Vero cell. In some embodiments, the host cell is a complementing host cell.

[0078] Other aspects of the present disclosure relate to a method of collecting a herpes simplex virus, the method comprising: (a) contacting a complementing host cell with any of the recombinant nucleic acids described herein; and (b) collecting the herpes simplex virus generated by the complementing host cell.

[0079] Other aspects of the present disclosure relate to a method of collecting a herpes simplex virus, the method comprising; (a) culturing a host cell comprising any of the recombinant nucleic acids described herein; and (b) collecting the herpes simplex virus generated by the host cell.286A97680.DOCXAttorney Docket No.: 10423-2600083 BRIEF DESCRIPTION OF THE DRAWINGS

[0080] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the Office upon request and payment of the necessary fee.

[0081] FIGS. 1A-1O show schematics of wild-type and modified herpes simplex virus genomes. FIG. 1 A shows a wild-type herpes simplex virus genome. FIG. IB shows a modified herpes simplex virus genome comprising deletions of the coding sequences of ICP4 (both copies) and ICP22, with a polynucleotide containing the coding sequence of a first human collagen or elastin polypeptide operably linked to a heterologous promoter integrated at each of the ICP4 loci. FIG. 1C shows a modified herpes simplex virus genome comprising deletions of the coding sequence of ICP4 (both copies), with a polynucleotide containing the coding sequence of a first human collagen or elastin polypeptide operably linked to a heterologous promoter integrated at each of the ICP4 loci. FIG. ID shows a modified herpes simplex virus genome comprising deletions of the coding sequences of ICP4 (both copies) and ICP22, with a polynucleotide containing 1) the coding sequence of a first human collagen or elastin polypeptide operably linked to a first heterologous promoter, and 2) the coding sequence of a second human collagen or elastin polypeptide operably linked to a second heterologous promoter, integrated at each of the ICP4 loci. Both the first and second human collagen or elastin polypeptides are encoded on the same strand of DNA. FIG. IE shows a modified herpes simplex virus genome comprising deletions of the coding sequence of ICP4 (both copies), with a polynucleotide containing 1) the coding sequence of a first human collagen or elastin polypeptide operably linked to a first heterologous promoter, and 2) the coding sequence of a second human collagen or elastin polypeptide operably linked to a second heterologous promoter, integrated at each of the ICP4 loci. Both the first and second human collagen or elastin polypeptides are encoded on the same strand of DNA. FIG. IF shows a modified herpes simplex virus genome comprising deletions of the coding sequences of ICP4 (both copies) and ICP22, with a polynucleotide containing 1) the coding sequence of a first human collagen or elastin polypeptide operably linked to a first heterologous promoter, and 2) the coding sequence of a second human collagen or elastin polypeptide operably linked to a second heterologous promoter, integrated at each of the ICP4 loci. The first and second human collagen or elastin polypeptides are encoded on opposite strands of DNA. FIG. 1G shows a modified herpes simplex virus genome comprising deletions of the coding sequence of ICP4 (both copies), with a polynucleotide containing 1) the coding sequence of a first human collagen or elastin296A97680.DOCXAttorney Docket No.: 10423-2600083 polypeptide operably linked to a first heterologous promoter, and 2) the coding sequence of a second human collagen or elastin polypeptide operably linked to a second heterologous promoter, integrated at each of the ICP4 loci. The first and second human collagen or elastin polypeptides are encoded on opposite strands of DNA. FIG. 1H shows a modified herpes simplex virus genome comprising deletions of the coding sequences of ICP4 (both copies) and ICP22, with a polynucleotide encoding a polycistronic mRNA operably linked to a heterologous promoter integrated at each of the ICP4 loci. The polycistronic mRNA contains the coding sequence of a first human collagen or elastin polypeptide and a second human collagen or elastin polypeptide separated by an internal ribosomal entry site (IRES). FIG. II shows a modified herpes simplex virus genome comprising deletions of the coding sequence of ICP4 (both copies), with a polynucleotide encoding a polycistronic mRNA operably linked to a heterologous promoter integrated at each of the ICP4 loci. The polycistronic mRNA contains the coding sequence of a first human collagen or elastin polypeptide and a second human collagen or elastin polypeptide separated by an internal ribosomal entry site (IRES).FIG. 1J shows a modified herpes simplex virus genome comprising deletions of the coding sequences of ICP4 (both copies) and ICP22, with a polynucleotide containing the coding sequence of a chimeric polypeptide operably linked to a heterologous promoter integrated at each of the ICP4 loci. The chimeric polypeptide comprises the amino acid sequence of a first human collagen or elastin polypeptide and second human collagen or elastin polypeptide separated by a cleavable linker. FIG. IK shows a modified herpes simplex virus genome comprising deletions of the coding sequence of ICP4 (both copies), with a polynucleotide containing the coding sequence of a chimeric polypeptide operably linked to a heterologous promoter integrated at each of the ICP4 loci. The chimeric polypeptide comprises the amino acid sequence of a first human collagen or elastin polypeptide and second human collagen or elastin polypeptide separated by a cleavable linker. FIG. IL shows a modified herpes simplex virus genome comprising deletions of the coding sequences of ICP4 (both copies) and ICP22, with a first polynucleotide containing the coding sequence of a first human collagen or elastin polypeptide operably linked to a heterologous promoter integrated at each of the ICP4 loci, and a second polynucleotide containing the coding sequence of a second human collagen or elastin polypeptide operably linked to a heterologous promoter integrated at the ICP22 locus. FIG. IM shows a modified herpes simplex virus genome comprising deletions of the coding sequences of ICP4 (both copies), ICP22, and UL41, with a first polynucleotide containing the coding sequence of a first human collagen or elastin polypeptide operably linked to a heterologous promoter integrated at each of the ICP4 loci, and a second polynucleotide 306A97680.DOCXAttorney Docket No.: 10423-2600083 containing the coding sequence of a second human collagen or elastin polypeptide operably linked to a heterologous promoter integrated at the UL41 locus. FIG. IN shows a modified herpes simplex virus genome comprising deletions of the coding sequences of ICP4 (both copies) and UL41, with a first polynucleotide containing the coding sequence of a first human collagen or elastin polypeptide operably linked to a heterologous promoter integrated at each of the ICP4 loci, and a second polynucleotide containing the coding sequence of a second human collagen or elastin polypeptide operably linked to a heterologous promoter integrated at the UL41 locus. FIG. IO shows a modified herpes simplex virus genome comprising deletions of the coding sequences of ICP4 (both copies) and ICP22, with a first polynucleotide containing the coding sequence of a human collagen polypeptide operably linked to a heterologous promoter integrated at each of the ICP4 loci, and a second polynucleotide containing the coding sequence of a human elastin polypeptide operably linked to a heterologous promoter integrated at the ICP22 locus.

[0082] FIGS. 2A-2C show human COL1A1 and COL1A2 nucleic acid and protein analyses in Vero cells infected with the indicated clones of HSV encoding COL1A1 alone (inserted into the ICP4 loci) or COL1A1 and COL1A2 (inserted into the ICP4 and ICP22 loci, respectively). FIG. 2A shows the levels of human COL1A1 transcripts present in Vero cells 5 days after infection with the indicated HSV clones, as determined by qRT-PCR analysis. Data is presented for two replicates ± SEM. FIG.2B shows the levels of human COL1A2 transcripts present in Vero cells 5 days after infection with the indicated HSV clones, as determined by qRT-PCR analysis. Data is presented for two replicates ± SEM. FIG. 2C shows western blot analysis of human COL1A1 and COL1A2 protein expression in Vero cells 5 days after infection with the indicated COL1A1 / COL1A2 positive clones, as determined by qRT-PCR. Uninfected (mock) Vero cells were used as a negative control; GAPDH was used as a loading control.

[0083] FIG. 3 shows western blot analysis of human COL1A1 and COL1A2 protein expression in Vero cells 5 days after infection with an HSV isolate encoding a COL1A1-IRES-COL1A2 sequence (IRES-Isolate 6) inserted into the ICP4 loci. Infection with an isolate that does not contain the IRES construct (no insertion) was used as a negative control; GAPDH was used as a loading control.

[0084] FIGS. 4A-4B show human COL3 nucleic acid and protein analyses in immortalized human keratinocytes (HaCaTs) infected with HSV-COL3. FIG. 4A shows the levels of human COL3A1 transcripts present in immortalized human keratinocytes (HKs) after infection with HSV-COL3 at the indicated MOIs. Uninfected (mock) and HSV-mCherry-infected (mCherry)316A97680.DOCXAttorney Docket No.: 10423-2600083 cells were used as negative controls. Data is presented for two replicates ± SEM. FIG. 4B shows representative immunofluorescence images of human COL3 protein expression in immortalized human keratinocytes 48 hours after infection with HSV-COL3 at the indicated MOIs. Uninfected (mock) cells were used as negative controls.

[0085] FIGS. 5A-5B show human COL3 nucleic acid and protein analyses in immortalized human dermal fibroblasts (HDFs) infected with HSV-COL3. FIG. 5A shows the levels of human COL3A1 transcripts present in immortalized human dermal fibroblasts (HDFs) after infection with HSV-COL3 at the indicated MOIs. Uninfected (mock) and HSV-mCherry-infected (mCherry) cells were used as negative controls. Data is presented for two replicates ± SEM. FIG. 5B shows representative immunofluorescence images of human COL3 protein expression in immortalized human dermal fibroblasts 48 hours after infection with HSV-COL3 at the indicated MOIs. Uninfected (mock) cells were used as negative controls.

[0086] FIGS. 6A-6D show human COL3 nucleic acid and protein analyses in aged primary human fibroblasts (HDFs), sourced from two different vendors, infected with HSV-COL3 at the indicated MOIs. FIG.6A shows the levels of human COL3A1 transcripts present in primary HDFs harvested from either a 65-year-old female patient or a 73-year-old male patient (vendor 1) after infection with HSV-COL3 at the indicated MOIs. Uninfected (mock) cells were used as a negative control. Data is presented for two replicates ± SEM. FIG. 6B shows western blot analysis of human COL3A1 protein expression in primary HDFs harvested from a 73-year-old male patient (vendor 1) after infection with HSV-COL3 at the indicated MOIs. Uninfected (mock) cells were used as a negative control; recombinant human COL3A1 (rCOL3Al) was used as a positive control; GAPDH was used as a loading control. FIG. 6C shows the levels of human COL3A1 transcripts present in primary HDFs harvested from either a 75-year-old female patient or a 73-year-old male patient (vendor 2) after infection with HSV-COL3 at the indicated MOIs. Uninfected (mock) cells were used as a negative control. Data is presented for two replicates ± SEM. FIG. 6D shows western blot analysis of human COL3A1 protein expression in primary HDFs harvested from a 75-year-old female patient (vendor 2) after infection with HSV-COL3 at the indicated MOIs. Uninfected (mock) cells were used as a negative control; recombinant human COL3A1 (rCOL3Al) was used as a positive control; GAPDH was used as a loading control.

[0087] FIGS. 7A-7B show human COL3 nucleic acid and protein analyses in immortalized human dermal fibroblasts (HDFs) upon UV exposure. FIG. 7A shows the concentration of COL3 secreted into the supernatant of cultured HDFs 24 hours after exposure to various dosages and times of UV light, as assessed by ELISA. Supernatant collected from non-UV 326A97680.DOCXAttorney Docket No.: 10423-2600083 exposed (-UV) HDFs cultured in parallel was used as a control. FIG. 7B shows the levels of human COL3A1 transcripts present in UV-exposed immortalized human dermal fibroblasts (HDFs) after infection with HSV-C0L3 at the indicated MOIs. Uninfected (mock) and HSV-mCherry-infected (mCherry) cells were used as negative controls. Data is presented for two replicates ± SEM.

[0088] FIGS. 8A-8C show COL3 nucleic acid and protein analyses of skin biopsies taken from control- or HSV-COL3 -treated young (6-8-week-old) and old (~ 13 -months-old) C57BL / 6 mice 48 hours after intradermal application. FIG. 8A shows the levels of human COL3A1 DNA present in skin biopsies taken from young and old mice 48 hours after being intradermally administered either HSV-COL3 or vehicle control, as assessed by qPCR analysis. FIG.8B shows the levels of human COL3A1 transcripts present in skin biopsies taken from young and old mice 48 hours after being intradermally administered either HSV-COL3 or vehicle control, as assessed by qRT-PCR analysis. For each condition in the qPCR and qRT-PCR analysis, data is presented as the average of four tissue samples (two replicates / tissue sample) ± SEM. FIG. 8C shows representative immunofluorescence images of human COL3 expression in skin biopsies taken from young and old mice 48 hours after being intradermally administered HSV-COL3. A young mouse intradermally administered vehicle alone was used as a negative control. DAPI staining was used to visualize nuclei.

[0089] FIG. 9 depicts the colocalization by immunofluorescence staining of human COL3 and ELN protein expression in mammalian cells transduced with a modified herpes simplex virus encoding COL3 and ELN (HSV-COL3ZELN). Representative images of IF staining of human COL3 (green) and human elastin (ELN; red) in Vero cells. Nuclei were visualized via DAPI staining (blue).

[0090] FIGS. 10A-10B show genome (qPCR; FIG. 10A) and transcript (qRT-PCR; FIG.10B) in healthy human fibroblasts and keratinocytes transduced with a modified herpes simplex virus encoding COL3 and ELN (HSV-COL3ZELN).

[0091] FIGS. 11A-11B depict genome (qPCR; FIG. HA) and transcript (qRT-PCR; FIG.11B) in primary aged human fibroblasts transduced with a modified herpes simplex virus encoding COL3 (HSV-COL3), ELN (HSV-ELN), or COL3 and ELN (HSV-COL3 / ELN).

[0092] FIG 12 shows western blot detection of COL3 in cell culture supernatants harvested from primary young and aged human dermal fibroblasts transduced with a modified herpes simplex virus encoding COL3 and ELN (HSV-COL3ZELN) at a multiplicity of infection (MOI) of 0.3, 1, or 3. Lanes 1-4 young fibroblasts; lanes 5-8 aged fibroblasts; lane 1 mock; lanes 2336A97680.DOCXAttorney Docket No.: 10423-2600083 and 6 HSV-C0L3 / ELN MOI 0.3; lanes 3 and 7 HSV-COL3 / ELN MOI 1; lanes 4 and 8 HSV-COL3 / ELN MOI 3; lane 9 ladder.

[0093] FIGS. 13A-13B depict western blot detection of ELN in cell lysates (FIG. 13A) and dose-dependent ELN secretion by ELISA in cell culture supernatants (FIG. 13B) harvested from primary young and aged human dermal fibroblasts transduced with a modified herpes simplex virus encoding COL3 and ELN (HSV-COL3 / ELN) at a multiplicity of infection (MOI) of 0.3, 1, 3, or 5.

[0094] FIGS. 14A-14D show viability in primary young (FIG. 14A and FIG. 14C) and aged (FIG. 14B and FIG. 14D) human dermal fibroblasts transduced with a modified herpes simplex virus encoding COL3 and ELN (HSV-COL3 / ELN) at a multiplicity of infection (MOI) of 0.3, 1, or 3 for 24 hours (FIGS. 14A-14B) or 48 hours (FIGS. 14C-14D).

[0095] FIGS. 15A-15B depict genome (qPCR; FIG. 15A) and transcript (qRT-PCR; FIG.15B) in skin sections harvested from immunocompetent mice administered a modified herpes simplex virus encoding COL3 and ELN (HSV-COL3 / ELN) for 24, 48, 72, 120, or 168 hours post infection (hpi).

[0096] FIG. 16 shows histology of skin sections harvested from immunocompetent mice administered a modified herpes simplex virus encoding COL3 and ELN (HSV-COL3ZELN). Representative images of hematoxylin and eosin (H&E) stained skin sections.

[0097] FIGS. 17A-17B depict a summary of an embodiment of the administration method described herein using a modified herpes simplex virus to a target area e.g., the decollete) of a subject before (FIG. 17A) and after (FIG. 17B) applying a grid e.g. a triangular shaped grid) having one or more openings to the target area of the subject.

[0098] FIGS. 18A-18B show a top view of a grid e.g. a triangular shaped grid) having one or more openings for applying markings to a target area e.g., the decollete) of a subject.

[0099] FIGS. 19A-19F depict results from an open-label trial that evaluated the safety and efficacy of a modified herpes simplex virus encoding COL3 (HSV-COL3) following microdepot administration as measured by a 5-point Global Aesthetic Improvement Scale (GAIS) and Subject Satisfaction Questionnaire (SSQ). FIG. 19A shows subject (left) and investigator (right) assessed GAIS results for wrinkles / lines at one and two months following initial administration of HSV-COL3. n=18 for each timepoint. FIG. 19B depicts subject satisfaction responder rate (defined as subject satisfaction increase of one or more points) of dynamic wrinkles at two months following initial administration of HSV-COL3. n=18. FIG. 19C shows subject (left) and investigator (right) assessed GAIS responder rates (defined as GAIS scores of +1 or +2) by attribute (e.g., crepiness, elasticity, hydration, radiance, texture) at one and two 346A97680.DOCXAttorney Docket No.: 10423-2600083 months following initial administration of HSV-COL3. n=17-18 for each timepoint. FIGS.19D-19F depict representative images of a subject’s decollete at baseline and two months following initial administration of HSV-COL3.

[0100] FIGS.20A-20G depict results from a randomized, double-blind, placebo-controlled trial that evaluated the safety and preliminary efficacy of a modified herpes simplex virus encoding COL3 and ELN (HSV-COL3 / ELN) following micro-depot administration as measured by a 5-point Global Aesthetic Improvement Scale (GAIS) and Subject Satisfaction Questionnaire (SSQ). FIG. 20A shows investigator assessed GAIS results for lines / wrinkles at one, two, and three months following initial administration of HSV-COL3 / ELN or placebo. n=ll for HSV-COL3 / ELN; n=7 for placebo. FIG. 20B shows subject assessed GAIS results for lines / wrinkles at one, two, and three months following initial administration of HSV-COL3 / ELN or placebo. n=ll for HSV-COL3 / ELN; n=7 for placebo. FIG.20C depicts subject satisfaction responder rate (defined as subject satisfaction increase of one or more points) of dynamic wrinkles at one, two, and three months following initial administration of HSV-COL3 / ELN or placebo. n=ll for HSV-COL3 / ELN; n=7 for placebo. FIG. 20D shows investigator assessed GAIS responder rates (defined as GAIS scores of +1 or +2) by attribute (e.g., elasticity, crepiness, hydration, radiance, texture) at one, two, and three months following initial administration of HSV-COL3 / ELN or placebo. n=10-ll for HSV-COL3 / ELN; n=7 for placebo. FIG. 20E shows subject assessed GAIS responder rates (defined as GAIS scores of +1 or +2) by attribute (e.g., elasticity, crepiness, hydration, radiance, texture) at one, two, and three months following initial administration of HSV-COL3 / ELN or placebo. n=10-ll for HSV-COL3 / ELN; n=7 for placebo. FIGS. 20F-20G depict representative images of a subject’s decollete at baseline and three months following initial administration of HSV-COL3 / ELN.DETAILED DESCRIPTION

[0101] In some embodiments, the present disclosure relates to recombinant nucleic acids (c.g, recombinant herpes viral genomes) encoding one or more cosmetic proteins, and to uses of these recombinant nucleic acids in viruses (e.g., in a herpes virus), compositions, formulations, medicaments, and / or methods for delivering one or more cosmetic proteins to the skin, such as onto, into, and / or through the skin (e.g., to the dermal ECM). In some embodiments, the present disclosure relates to recombinant nucleic acids (e.g., recombinant herpes viral genomes) encoding one or more cosmetic proteins, and to uses of these recombinant nucleic acids in viruses (e.g., in a herpes virus), compositions, formulations,356A97680.DOCXAttorney Docket No.: 10423-2600083 medicaments, and / or methods in order to increase, augment, and / or supplement one or more dermal ECM proteins (e.g., one or more collagen proteins). In some embodiments, the present disclosure relates to recombinant nucleic acids (e.g., recombinant herpes viral genomes) encoding one or more cosmetic proteins, and to uses of these recombinant nucleic acids in viruses (e.g., in a herpes virus), compositions, formulations, medicaments, and / or methods in the aesthetic context (e.g., to reduce one or more dermatological signs of aging). In some embodiments, the present disclosure relates to compositions comprising a recombinant herpes viral vector and methods comprising the delivery of the recombinant herpes viral vector onto, into, and / or through the skin of a mammal, wherein the recombinant herpes viral vector comprises a promoter operable in a mammalian cell and a heterologous nucleic acid which is expressed to achieve a cosmetic effect in mammalian skin. The heterologous nucleic acid may be delivered to a mammalian target skin cell of a mammal, comprising contacting the epidermis, dermis, or subcutaneous tissue of the mammal with the composition comprising the recombinant herpes viral vector, under conditions whereby the recombinant herpes viral vector is transported onto, into, and / or through the epidermis, dermis or subcutaneous tissue and introduced into the target skin cell, where it is expressed Without wishing to be bound by theory, it is believed that administering one or more of the recombinant nucleic acids, viruses, and / or formulations described herein to an individual will allow for increased production of functional dermal ECM proteins (e.g., human collagen) in the individual. Furthermore, without wishing to be bound by theory, it is believed that increasing, augmenting, and / or supplementing the levels of cosmetic proteins in an individual by administering one or more of the recombinant nucleic acids, viruses, and / or formulations described herein will lead to at least one of: 1) the enhancement, augmentation, and / or supplementation of soft tissue; 2) the improvement of skin quality, condition, and / or appearance; 3) the reduction of one or more superficial depressions in the skin (e.g., wrinkles); 4) the improvement of texture, smoothness, elasticity, pigmentation, thinness, hydration, and / or tension of the skin; and / or 5) the reduction of one or more dermatological signs of aging. Ultimately, without wishing to be bound by theory, it is believed that the recombinant nucleic acids, viruses, compositions, and methods described herein provide a novel strategy for delivering functional cosmetic proteins in aesthetic settings.

[0102] The following description sets forth exemplary methods, parameters, and the like. It should be recognized, however, that such a description is not intended as a limitation on the scope of the present disclosure but is instead provided as a description of exemplary embodiments.366A97680.DOCXAttorney Docket No.: 10423-2600083 I. General techniques

[0103] The techniques and procedures described or referenced herein are generally well understood and commonly employed using conventional methodology by those skilled in the art, such as, for example, the widely utilized methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual 3d edition (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; Current Protocols in Molecular Biology (F.M. Ausubel, et al. eds., (2003)); the senes Methods in Enzymology (Academic Press, Inc.): PCR 2: A Practical Approach (M.J. MacPherson, B.D. Hames and G.R. Taylor eds. (1995)), Harlow and Lane, eds. (1988); Oligonucleotide Synthesis (M.J. Gait, ed., 1984); Methods in Molecular Biology, Humana Press; Cell Biology: A Laboratory Notebook (J.E. Cellis, ed., 1998) Academic Press; Animal Cell Culture (R.I. Freshney), ed., 1987); Introduction to Cell and Tissue Culture (J.P. Mather and P.E. Roberts, 1998) Plenum Press; Cell and Tissue Culture: Laboratory Procedures (A. Doyle, J.B. Griffiths, and D.G. Newell, eds., 1993-8) J. Wiley and Sons; Gene Transfer Vectors for Mammalian Cells (J.M. Miller and M.P. Calos, eds., 1987); PCR: The Polymerase Chain Reaction, (Mullis et al., eds., 1994); Short Protocols in Molecular Biology (Wiley and Sons, 1999).II. Definitions

[0104] Before describing the present disclosure in detail, it is to be understood that the present disclosure is not limited to particular compositions or biological systems, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0105] As used herein, the singular forms “a”, “an” and “the” include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to “a molecule” optionally includes a combination of two or more such molecules, and the like.

[0106] As used herein, the term “and / or” may include any and all combinations of one or more of the associated listed items. For example, the term “a and / or b” may refer to “a alone”, “b alone”, “a or b”, or “a and b”; the term “a, b, and / or c” may refer to “a alone”, “b alone”, “c alone”, “a or b”, “a or c”, “b or c”, “a, b, or c”, “a and b”, “a and c”, “b and c”, or “a, b, and c”; etc.

[0107] As used herein, the term “about” refers to the usual error range for the respective value readily known to the skilled person in this technical field. Reference to “about” a value or parameter herein includes (and describes) embodiments that are directed to that value or parameter per se.376A97680.DOCXAttorney Docket No.: 10423-2600083

[0108] It is understood that aspects and embodiments of the present disclosure include “comprising”, “consisting”, and “consisting essentially of’ aspects and embodiments.

[0109] As used herein, the terms “polynucleotide”, "nucleic acid sequence", "nucleic acid", and variations thereof shall be generic to polydeoxyribonucleotides (containing 2-deoxy-D-ribose), to polyribonucleotides (containing D-ribose), to any other type of polynucleotide that is an N-glycoside of a purine or pyrimidine base, and to other polymers containing non-nucleotidic backbones, provided that the polymers contain nucleobases in a configuration that allows for base pairing and base stacking, as found in DNA and RNA. Thus, these terms include known types of nucleic acid sequence modifications, for example, substitution of one or more of the naturally occurring nucleotides with an analog, and inter-nucleotide modifications.

[0110] As used herein, a nucleic acid is “operatively linked” or “operably linked” when it is placed into a functional relationship with another nucleic acid sequence. For example, a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation. Generally, “operatively linked” or “operably linked” means that the DNA sequences being linked are contiguous.[OHl] As used herein, the term “vector” refers to discrete elements that are used to introduce heterologous nucleic acids into cells for either expression or replication thereof. An expression vector includes vectors capable of expressing nucleic acids that are operatively linked with regulatory sequences, such as promoter regions, that are capable of effecting expression of such nucleic acids. Thus, an expression vector may refer to a DNA or RNA construct, such as a plasmid, a phage, recombinant virus or other vector that, upon introduction into an appropriate host cell, results in expression of the nucleic acids. Appropriate expression vectors are well known to those of skill in the art and include those that are replicable in eukaryotic cells, and those that remain episomal or those which integrate into the host cell genome.

[0112] As used herein, an “open reading frame” or “ORF” refers to a continuous stretch of nucleic acids, either DNA or RNA, that encode a protein or polypeptide. Typically, the nucleic acids comprise a translation start signal or initiation codon, such as ATG or AUG, and a termination codon.

[0113] As used herein, an “untranslated region” or “UTR” refers to untranslated nucleic acids at the 5’ and / or 3’ ends of an open reading frame. The inclusion of one or more UTRs in a polynucleotide may affect post-transcriptional regulation, mRNA stability, and / or translation of the polynucleotide.386A97680.DOCXAttorney Docket No.: 10423-2600083

[0114] As used herein, the term “transgene” refers to a polynucleotide that is capable of being transcribed into RNA and translated and / or expressed under appropriate conditions, after being introduced into a cell. In some aspects, it confers a desired property to a cell into which it was introduced, or otherwise leads to a desired cosmetic, therapeutic, or diagnostic outcome.

[0115] As used herein, the terms “polypeptide,” “protein,” and “peptide” are used interchangeably and may refer to a polymer of two or more amino acids.

[0116] As used herein, a “subject”, “host”, or an “individual” refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, horses, cats, cows, as well as animals used in research, such as mice, rats, hamsters, rabbits, and non-human primates, etc. In some embodiments, the mammal is human.

[0117] As used herein, the terms “pharmaceutical formulation” or “pharmaceutical composition” refer to a preparation which is in such a form as to permit the biological activity of the active ingredient(s) to be effective, and which contains no additional components which are unacceptably toxic to a subject to which the composition or formulation would be administered. “Pharmaceutically acceptable” excipients e.g., vehicles, additives) are those which can reasonably be administered to a subject to provide an effective dose of the active ingredient(s) employed.

[0118] As used herein, “cutaneous administration” or “cutaneously administering” refers to the delivery of a composition to a subject by contacting, directly or otherwise, a formulation comprising the composition to all (“systemic”) or a portion (“topical”) of the skin of a subject. The term encompasses several routes of administration including, but not limited to, topical and transdermal. Topical administration may be used as a means to deliver a composition to the epidermis or dermis of a subject, or to specific strata thereof.

[0119] As used herein, “treatment” refers to clinical intervention designed to alter the natural course of the individual or cell being treated during the course of clinical pathology. Desirable effects of treatment include decreasing the rate of disease / disorder / defect progression, ameliorating or palliating the disease / disorder / defect state, and remission or improved prognosis. For example, an individual is successfully “treated” if one or more symptoms associated with dermatological aging are reduced, mitigated, or eliminated, including the reduction or elimination of wrinkles.

[0120] As used herein, the term “delaying progression of’ a disease / disorder / defect refers to deferring, hindering, slowing, retarding, stabilizing, and / or postponing development of the disease / disorder / defect (e.g., skin wrinkles). This delay can be of varying lengths or time, depending on the history of the disease / disorder / defect and / or the individual being treated. As 396A97680.DOCXAttorney Docket No.: 10423-2600083 is evident to one of ordinary skill in the art, a sufficient or significant delay can, in effect, encompass prevention, in that the individual does not develop the disease / disorder / defect.III. Recombinant Nucleic Acids

[0121] Certain aspects of the present disclosure relate to recombinant nucleic acids (e.g., isolated recombinant nucleic acids) comprising one or more polynucleotides (e.g., one or more, two or more, three or more, four or more, five or more, ten or more, etc.) encoding a cosmetic protein. Any suitable cosmetic protein described herein or known in the art may be encoded by the polynucleotides of the present disclosure, including, for example, collagen proteins, fibronectins, elastins, lumicans, vitronectins / vitronectin receptors, laminins, neuromodulators, fibrillins, additional dermal ECM proteins, etc. In some embodiments, the cosmetic protein is a structural extracellular matrix protein (e.g., a collagen, elastin, fibronectin, laminin, fibrillin, etc.). In some embodiments, the cosmetic protein is a collagen, elastin, fibronectin, laminin, or hyaluronan synthase protein (e.g., a human collagen, elastin, fibronectin, laminin, or hyaluronan synthase protein).

[0122] In some embodiments, the present disclosure relates to recombinant nucleic acids (e.g., isolated recombinant nucleic acids) comprising one or more polynucleotides (e.g., one or more, two or more, three or more, four or more, five or more, ten or more, etc.) encoding a collagen protein. In some embodiments, the collagen protein is a human collagen protein. In some embodiments, the present disclosure relates to recombinant nucleic acids comprising one or more polynucleotides encoding a homotrimeric collagen (e.g., a homotrimeric human collagen, such as human Collagen 3 (e.g., comprising three COL3 Al (COL3) polypeptides) or human Collagen 7 (e.g., comprising three COL7A1 (COL7) polypeptides). In some embodiments, the present disclosure relates to recombinant nucleic acids comprising one or more polynucleotides encoding a heterotrimeric collagen (e.g., a heterotrimeric human collagen, such as human Collagen 1 (e.g., comprising two COL1A1 (COL1-1) polypeptides and one COL1 A2 (COL1-2) polypeptide) or human Collagen 4 (e.g., comprising two COL4A1 (COL4-1) polypeptides and one COL4A2 (COL4-2) polypeptide). In some embodiments, the present disclosure relates to recombinant nucleic acids comprising one or more polynucleotides encoding a homotrimeric collagen and a heterotrimeric collagen (e.g., a recombinant nucleic acid comprising one or more polynucleotides encoding a human Collagen 1 and a human Collagen 3). In some embodiments, the present disclosure relates to recombinant nucleic acids comprising one or more polynucleotides encoding human Collagen 1. In some embodiments, the present disclosure relates to recombinant nucleic acids comprising one or more polynucleotides encoding human Collagen 3.406A97680.DOCXAttorney Docket No.: 10423-2600083

[0123] In some embodiments, the present disclosure relates to recombinant nucleic acids comprising a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein (e.g., a first human collagen protein). In some embodiments, the first polypeptide consists essentially of or consists of the first cosmetic protein (e.g., consists essentially of or consists of a first human collagen protein). In some embodiments, the present disclosure relates to recombinant nucleic acids comprising a first polynucleotide encoding a first polypeptide comprising: a first cosmetic protein (e.g., a first human collagen protein), a linker polypeptide, and a further cosmetic protein (e.g., a further human collagen protein). In some embodiments, the first and further cosmetic proteins (e.g., the first and further human collagen proteins) are the same. In some embodiments, the first and further cosmetic proteins (e.g., the first and further human collagen proteins) are different. In some embodiments, the linker polypeptide is a cleavable linker polypeptide.

[0124] In some embodiments, the present disclosure relates to recombinant nucleic acids comprising a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein (e.g., a first human collagen protein), wherein the first polynucleotide encodes a polycistronic mRNA comprising: a first open reading frame (ORF) encoding the first polypeptide, an internal ribosomal entry site (IRES), and a second ORF encoding an additional cosmetic protein (e.g., an additional human collagen protein). In some embodiments, the first and additional cosmetic proteins (e.g., the first and additional human collagen proteins) are the same. In some embodiments, the first and additional cosmetic proteins (e.g., the first and additional human collagen proteins) are different.

[0125] In some embodiments, the present disclosure relates to recombinant nucleic acids comprising a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein (e.g., a first human collagen protein), and a second polynucleotide encoding a second cosmetic protein (e.g., a second human collagen protein). In some embodiments, the first and second cosmetic proteins (e.g., the first and second human collagen proteins) are the same. In some embodiments, the first and second cosmetic proteins (e.g., the first and second human collagen proteins) are different.

[0126] In some embodiments, the present disclosure relates to recombinant nucleic acids comprising a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein (e.g., a first human collagen protein), and a second polynucleotide encoding a second cosmetic protein (e.g., a second human elastin protein).

[0127] In some embodiments, the recombinant nucleic acid is a vector. In some embodiments, the recombinant nucleic acid is a viral vector. In some embodiments, the 416A97680.DOCXAttorney Docket No.: 10423-2600083 recombinant nucleic acid is a herpes viral vector. In some embodiments, the recombinant nucleic acid is a herpes simplex virus amplicon. In some embodiments, the recombinant nucleic acid is a recombinant herpes virus genome. In some embodiments, the recombinant nucleic acid is a recombinant herpes simplex virus genome. In some embodiments, the recombinant herpes simplex virus genome is a recombinant herpes simplex virus type 1 (HSV-1) genome.Polynucleotides encoding cosmetic proteinsPolynucleotides encoding collagen proteins

[0128] In some embodiments, the present disclosure relates to a recombinant nucleic acid comprising one or more polynucleotides comprising the coding sequence of a collagen gene. The coding sequence of any collagen gene (including any isoform thereof) from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, human collagen genes (see e.g., NCBI Gene IDs: 1277, 1278, 1281, 1282, 1284, 1291, 1294, 1308, etc.), mouse collagen genes (see, e.g., NCBI Gene IDs: 12842, 12843, 12825, 12826, 12827, 12833, 12836, 12821, etc.), chimpanzee collagen genes (see e.g., NCBI Gene IDs: 104001053, 455117, 459815, 452689, 452661, 450204, 101056895, 101058306, etc.), rat collagen genes (see e.g., NCBI Gene IDs: 29393, 84352, 84032, 290905, 306628, 294337, 301012, 294027, etc.), rabbit collagen genes (see e.g., NCBI Gene IDs: 100347598, 100008997, 100009177, 100358256, 100358522, 100343947, 100356561, 100339335, etc.) etc. Methods of identifying collagen gene homologs / orthologs from additional species are known to one of ordinary skill in the art, including, for example, using a nucleic acid sequence alignment program such as the BLAST® blastn suite. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the collagen genes (and / or coding sequences thereof) described herein or known in the art.

[0129] In some embodiments, a polynucleotide of the present disclosure comprises a codon-optimized variant of the coding sequence of any of the collagen genes described herein or known in the art. In some embodiments, use of a codon-optimized variant of the coding sequence of a collagen gene increases stability and / or yield of heterologous expression (RNA and / or protein) of the encoded collagen protein in a target cell (such as a cell of the epidermis and / or dermis), as compared to the stability and / or yield of heterologous expression of a corresponding, non-codon-optimized, wild-type sequence. Any suitable method known in the art for performing codon optimization of a sequence for expression in one or more target cells 426A97680.DOCXAttorney Docket No.: 10423-2600083 (e.g., one or more human cells) may be used, including, for example, by the methods described by Fath et al. (PLoS One. 2011 Mar 3;6(3): el7596).

[0130] In some embodiments, the present disclosure relates to one or more polynucleotides (i.e., one or more first polynucleotides and / or one or more second polynucleotides) comprising the coding sequence of a human collagen gene. Any suitable human collagen gene (including any isoform thereof) known in the art may be encoded by a nucleic acid of the present disclosure, including, for example, a COL1A1 gene (see e.g., NCBI Gene ID: 1277; SEQ ID NO: 1), a COL1A2 gene (see e.g., NCBI Gene ID: 1278; SEQ ID NO: 3), a COL2A1 gene (see e.g., NCBI Gene ID: 1280), a COL3A1 gene (see e.g., NCBI Gene ID: 1281; SEQ ID NO: 5), a COL4A1 gene (see e.g., NCBI Gene ID: 1282; SEQ ID NO: 7), a COL4A2 gene (see e.g., NCBI Gene ID: 1284), a COL4A3 gene (see e.g., NCBI Gene ID: 1285), a COL4A4 gene (see e.g., NCBI Gene ID: 1286), a COL4A5 gene (see e.g., NCBI Gene ID: 1287), a COL4A6 gene (see e.g., NCBI Gene ID: 1288), a COL5A1 gene (see e.g., NCBI Gene ID: 1289), a COL5A2 gene (see e.g., NCBI Gene ID: 1290), a COL5A3 gene (see e.g., NCBI Gene ID: 50509), a COL6A1 gene (see e.g., NCBI Gene ID: 1291; SEQ ID NO: 9), a COL6A2 gene (see e.g., NCBI Gene ID: 1292), a COL6A3 gene (see e.g., NCBI Gene ID: 1293), a COL6A4 gene (see e.g., NCBI Gene ID: 344875), a COL6A5 gene (see e.g., NCBI Gene ID: 256076), a COL6A6 gene (see e.g., NCBI Gene ID: 131873), a COL7A1 gene (see e.g., NCBI Gene ID: 1294; SEQ ID NO: 10), a COL8A1 gene (see e.g., NCBI Gene ID: 1295), a COL9A1 gene (see e.g., NCBI Gene ID: 1297), a COL9A2 gene (see e.g., NCBI Gene ID: 1298), a COL9A3 gene (see e.g., NCBI Gene ID: 1299), a COL10A1 gene (see e.g., NCBI Gene ID: 1300), a COL11A1 gene (see e.g., NCBI Gene ID: 1301), a COL11A2 gene (see e.g., NCBI Gene ID: 1302), a COL12A1 gene (see e.g., NCBI Gene ID: 1303), a COL13A1 gene (see e.g., NCBI Gene ID: 1305), a COL14A1 gene (see e.g., NCBI Gene ID: 7373), a COL15A1 gene (see e.g., NCBI Gene ID: 1306), a COL16A1 gene (see e.g., NCBI Gene ID: 1307), a COL17A1 gene (see e.g., NCBI Gene ID: 1308; SEQ ID NO: 12), a COL18A1 gene (see e.g., NCBI Gene ID: 80781), a COL19A1 gene (see e.g., NCBI Gene ID: 1310), a COL20A1 gene (see e.g., NCBI Gene ID: 57642), a COL21A1 gene (see e.g., NCBI Gene ID: 81578), a COL22A1 gene (see e.g., NCBI Gene ID: 169044), a COL23A1 gene (see e.g., NCBI Gene ID: 91522), a COL24A1 gene (see e.g., NCBI Gene ID: 255631), a COL25A1 gene (see e.g., NCBI Gene ID: 84570), a COL26A1 gene (see e.g., NCBI Gene ID: 136227), a COL27A1 gene (see e.g., NCBI Gene ID: 85301), a COL28A1 gene (see e.g., NCBI Gene ID:340267), etc. In some embodiments, a polynucleotide (i.e., one or more first polynucleotides and / or one or more second polynucleotides) of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 436A97680.DOCXAttorney Docket No.: 10423-2600083 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the human collagen genes (and / or coding sequences thereof) described herein or known in the art.

[0131] In some embodiments, a polynucleotide (i.e., one or more first polynucleotides and / or one or more second polynucleotides) of the present disclosure comprises a codon-optimized variant of any of the human collagen genes described herein. In some embodiments, use of a codon-optimized variant of a human collagen gene increases stability and / or yield of heterologous expression (RNA and / or protein) of the human collagen in a target cell (such as a human keratinocyte or fibroblast), as compared to the stability and / or yield of heterologous expression of a corresponding non-codon-optimized, wild-type sequence.

[0132] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human COL1A1 gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 1 or SEQ ID NO: 2.

[0133] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 1 or SEQ ID NO: 2 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, at least 4000, but fewer than 4395, consecutive nucleotides of SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-4392 of SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-4392 of SEQ ID NO: 1 or SEQ ID NO: 2.446A97680.DOCXAttorney Docket No.: 10423-2600083

[0134] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human COL1A2 gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 3 or SEQ ID NO: 4. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 3 or SEQ ID NO: 4.

[0135] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 3 or SEQ ID NO: 4. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 3 or SEQ ID NO: 4 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, at least 4000, but fewer than 4101, consecutive nucleotides of SEQ ID NO: 3 or SEQ ID NO: 4. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-4098 of SEQ ID NO: 3 or SEQ ID NO: 4. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-4098 of SEQ ID NO: 3 or SEQ ID NO: 4.

[0136] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human COL3A1 gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 5 or SEQ ID NO: 6. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 5 or SEQ ID NO: 6.

[0137] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 5 or SEQ ID NO: 6. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 5 or SEQ ID NO: 6 is a polynucleotide that has at least 25, at least 50, at least 75, at least 456A97680.DOCXAttorney Docket No.: 10423-2600083 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, at least 4000, but fewer than 4401, consecutive nucleotides of SEQ ID NO: 5 or SEQ ID NO: 6. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-4398 of SEQ ID NO: 5 or SEQ ID NO: 6. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-4398 of SEQ ID NO: 5 or SEQ ID NO: 6.

[0138] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human COL4A1 gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 7 or SEQ ID NO: 8. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 7 or SEQ ID NO: 8.

[0139] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 7 or SEQ ID NO: 8. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 7 or SEQ ID NO: 8 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, at least 4000, at least 4500, at least 5000, but fewer than 5010, consecutive nucleotides of SEQ ID NO: 7 or SEQ ID NO: 8. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-5007 of SEQ ID NO: 7 or SEQ ID NO: 8. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-5007 of SEQ ID NO: 7 or SEQ ID NO: 8.466A97680.DOCXAttorney Docket No.: 10423-2600083

[0140] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human COL6A1 gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 9 or SEQ ID NO: 10.

[0141] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 9 or SEQ ID NO: 10 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, but fewer than 3087, consecutive nucleotides of SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-3084 of SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-3084 of SEQ ID NO: 9 or SEQ ID NO: 10.

[0142] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human COL7A1 gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 11 or SEQ ID NO: 12. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 11 or SEQ ID NO: 12.

[0143] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 11 or SEQ ID NO: 12. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 11 or SEQ ID NO: 12 is a polynucleotide that has at least 25, at least 50, at least 75, at 476A97680.DOCXAttorney Docket No.: 10423-2600083 least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, at least 4000, at least 4500, at least 5000, at least 5500, at least 6000, at least 6500, at least 7000, at least 7500, at least 8000, at least 8500, but fewer than 8835, consecutive nucleotides of SEQ ID NO: 11 or SEQ ID NO: 12. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-8832 of SEQ ID NO: 11 or SEQ ID NO: 12. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-8832 of SEQ ID NO: 11 or SEQ ID NO: 12.

[0144] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human COL17A1 gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 13 or SEQ ID NO: 14.

[0145] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 13 or SEQ ID NO: 14 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, at least 4000, but fewer than 4494, consecutive nucleotides of SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-4491 of SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, a polynucleotide of the486A97680.DOCXAttorney Docket No.: 10423-2600083 present disclosure comprises the sequence of nucleic acids 1-4491 of SEQ ID NO: 13 or SEQ ID NO: 14.

[0146] In some embodiments, a polynucleotide of the present disclosure encoding one or more human collagen proteins (e.g., a first human collagen protein, a further human collagen protein, an additional human collagen protein, and / or a second human collagen protein) has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NOS: 1-14. In some embodiments, a polynucleotide of the present disclosure encoding one or more human collagen proteins (e.g., a first human collagen protein, a further human collagen protein, an additional human collagen protein, and / or a second human collagen protein) comprises a sequence selected from SEQ ID NOS: 1-14.Polynucleotides encoding fibronectin proteins

[0147] In some embodiments, the present disclosure relates to a recombinant nucleic acid comprising one or more polynucleotides comprising the coding sequence of a fibronectin gene. The coding sequence of any fibronectin gene (including any isoform thereof) from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a human fibronectin gene (see e.g., NCBI Gene ID: 2335), a mouse fibronectin gene (see, e.g., NCBI Gene ID: 14268), a chimpanzee fibronectin gene (see e.g., NCBI Gene ID: 459926), a rat fibronectin gene (see e.g., NCBI Gene ID: 25661), a rabbit fibronectin gene (see e.g., NCBI Gene ID: 100328589), etc. Methods of identifying fibronectin gene homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the fibronectin genes (and / or coding sequences thereof) described herein or known in the art. In some embodiments, a polynucleotide of the present disclosure comprises a codon-optimized variant of any of the fibronectin genes (and / or coding sequences thereof) described herein or known in the art.

[0148] In some embodiments, the present disclosure relates to one or more polynucleotides (i.e., one or more first polynucleotides and / or one or more second polynucleotides) comprising the coding sequence of a human fibronectin gene. In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human FN1 gene (or a codon- 496A97680.DOCXAttorney Docket No.: 10423-2600083 optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 35 or SEQ ID NO: 36. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 35 or SEQ ID NO: 36.

[0149] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 35 or SEQ ID NO: 36. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 35 or SEQ ID NO: 36 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, at least 4000, at least about 4500, at least about 5000, at least about 5500, at least about 6000, at least about 6500, at least about 7000, but fewer than 7434, consecutive nucleotides of SEQ ID NO: 35 or SEQ ID NO: 36. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-7431 of SEQ ID NO: 35 or SEQ ID NO: 36. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-7431 of SEQ ID NO: 35 or SEQ ID NO: 36.Polynucleotides encoding elastin proteins

[0150] In some embodiments, the present disclosure relates to a recombinant nucleic acid comprising one or more polynucleotides comprising the coding sequence of an elastin gene. The coding sequence of any elastin gene (including any isoform thereof) from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a human elastin gene (see e.g., NCBI Gene ID: 2006), a mouse elastin gene (see, e.g., NCBI Gene ID: 13717), a chimpanzee elastin gene (see e.g., NCBI Gene ID: 463943), a rat elastin gene (see e.g., NCBI Gene ID: 25043), a rabbit elastin gene (see e.g., NCBI Gene ID: 100344271), etc. Methods of identifying elastin gene homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 506A97680.DOCXAttorney Docket No.: 10423-2600083 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the elastin genes (and / or coding sequences thereof) described herein or known in the art. In some embodiments, a polynucleotide of the present disclosure comprises a codon-optimized variant of any of the elastin genes (and / or coding sequences thereof) described herein or known in the art.

[0151] In some embodiments, the present disclosure relates to one or more polynucleotides (z.e., one or more first polynucleotides and / or one or more second polynucleotides) comprising the coding sequence of a human elastin gene. In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human ELN gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 37 or SEQ ID NO: 38. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 37 or SEQ ID NO: 38.

[0152] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 37 or SEQ ID NO: 38. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 37 or SEQ ID NO: 38 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2250, but fewer than 2361, consecutive nucleotides of SEQ ID NO: 37 or SEQ ID NO: 38. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-2358 of SEQ ID NO: 37 or SEQ ID NO: 38. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-2358 of SEQ ID NO: 37 or SEQ ID NO: 38.Polynucleotides encoding lumican proteins

[0153] In some embodiments, the present disclosure relates to a recombinant nucleic acid comprising one or more polynucleotides comprising the coding sequence of a lumican gene.516A97680.DOCXAttorney Docket No.: 10423-2600083 The coding sequence of any lumican gene (including any isoform thereof) from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a human lumican gene (see e.g., NCBI Gene ID: 4060), a mouse lumican gene (see, e.g., NCBI Gene ID: 17022), a chimpanzee lumican gene (see e.g., NCBI Gene ID: 452119), a rat lumican gene (see e.g., NCBI Gene ID: 81682), a rabbit lumican gene (see e.g., NCBI Gene ID: 100008665), etc. Methods of identifying lumican gene homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the lumican genes (and / or coding sequences thereof) described herein or known in the art. In some embodiments, a polynucleotide of the present disclosure comprises a codon-optimized variant of any of the lumican genes (and / or coding sequences thereof) described herein or known in the art.

[0154] In some embodiments, the present disclosure relates to one or more polynucleotides (i.e., one or more first polynucleotides and / or one or more second polynucleotides) comprising the coding sequence of a human lumican gene. In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human LUM gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 39 or SEQ ID NO: 40. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 39 or SEQ ID NO: 40.

[0155] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 39 or SEQ ID NO: 40. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 39 or SEQ ID NO: 40 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, but fewer than 1017, consecutive nucleotides of SEQ ID NO: 39 or SEQ ID NO: 40. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 526A97680.DOCXAttorney Docket No.: 10423-2600083 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-1014 of SEQ ID NO: 39 or SEQ ID NO: 40. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-1014 of SEQ ID NO: 39 or SEQ ID NO: 40.Polynucleotides encoding vitronectin and vitronectin receptor proteins

[0156] In some embodiments, the present disclosure relates to a recombinant nucleic acid comprising one or more polynucleotides comprising the coding sequence of a vitronectin or vitronectin receptor gene. The coding sequence of any vitronectin or vitronectin receptor gene (including any isoform thereof) from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a human vitronectin or vitronectin receptor gene (see e.g., NCBI Gene IDs: 7448 and 3685), a mouse vitronectin or vitronectin receptor gene (see, e.g., NCBI Gene IDs: 22370 and 16410), a chimpanzee vitronectin or vitronectin receptor gene (see e.g., NCBI Gene IDs: 738261 and 459807), a rat vitronectin or vitronectin receptor gene (see e.g., NCBI Gene IDs: 29169 and 257645), a rabbit vitronectin or vitronectin receptor gene (see e.g., NCBI Gene IDs: 100009128 and 100008956), etc. Methods of identifying vitronectin or vitronectin receptor gene homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the vitronectin or vitronectin receptor genes (and / or coding sequences thereof) described herein or known in the art. In some embodiments, a polynucleotide of the present disclosure comprises a codon-optimized variant of any of the vitronectin or vitronectin receptor genes (and / or coding sequences thereof) described herein or known in the art.

[0157] In some embodiments, the present disclosure relates to one or more polynucleotides (i.e., one or more first polynucleotides and / or one or more second polynucleotides) comprising the coding sequence of a human vitronectin or vitronectin receptor gene. In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human VTN gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%536A97680.DOCXAttorney Docket No.: 10423-2600083 sequence identity to the sequence of SEQ ID NO: 41 or SEQ ID NO: 42. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 41 or SEQ ID NO: 42.

[0158] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 41 or SEQ ID NO: 42. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 41 or SEQ ID NO: 42 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least about 1250, but fewer than 1437, consecutive nucleotides of SEQ ID NO: 41 or SEQ ID NO: 42. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-1034 of SEQ ID NO: 41 or SEQ ID NO: 42. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-1034 of SEQ ID NO: 41 or SEQ ID NO: 42.Polynucleotides encoding laminin proteins

[0159] In some embodiments, the present disclosure relates to a recombinant nucleic acid comprising one or more polynucleotides comprising the coding sequence of a laminin gene. The coding sequence of any laminin gene (including any isoform thereof) from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, human laminin genes (see e.g., NCBI Gene IDs: 284217, 3908, 3909, 3910, 3911, 3912, 3913, 3914, 3915, 3918, and 10319), mouse laminin genes (see e.g., NCBI Gene IDs: 16774, 16780, and 16782), chimpanzee laminin genes (see e.g., NCBI Gene IDs: 455339, 469668, and 457571), rat laminin genes (see e.g., NCBI Gene IDs: 307582, 305078, and 192362), rabbit laminin genes (see e.g., NCBI Gene IDs: 100346886 and 100342905), etc. Methods of identifying laminin gene homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the laminin genes (and / or coding sequences thereof) described herein or known in the art. In some embodiments, a polynucleotide of the present 546A97680.DOCXAttorney Docket No.: 10423-2600083 disclosure comprises a codon-optimized variant of any of the laminin genes (and / or coding sequences thereof) described herein or known in the art.

[0160] In some embodiments, the present disclosure relates to one or more polynucleotides (z.e., one or more first polynucleotides and / or one or more second polynucleotides) comprising the coding sequence of a human laminin gene, such as a human LAMA1 gene (see e.g., NCBI Gene ID: 284217), a human LAMA2 gene (see e.g., NCBI Gene ID: 3908), a human LAMA3 gene (see e.g., NCBI Gene ID: 3909), a human LAMA4 gene (see e.g., NCBI Gene ID: 3910), a human LAMA5 gene (see e.g., NCBI Gene ID: 3911), a human LAMB1 gene (see e.g., NCBI Gene ID: 3912), a human LAMB2 gene (see e.g., NCBI Gene ID: 3913), a human LAMB3 gene (see e.g., NCBI Gene ID: 3914), a human LAMC1 gene (see e.g., NCBI Gene ID: 3915), a human LAMC2 gene see e.g., NCBI Gene ID: 3918), or a human LAMC3 gene see e.g., NCBI Gene ID: 10319).

[0161] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human LAMA3 gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 43 or SEQ ID NO: 44. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 43 or SEQ ID NO: 44.

[0162] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 43 or SEQ ID NO: 44. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 43 or SEQ ID NO: 44 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, at least 4000, at least about 4500, at least about 5000, but fewer than 5175, consecutive nucleotides of SEQ ID NO: 43 or SEQ ID NO: 44. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-5172 of SEQ ID NO: 43 or SEQ ID NO: 44. In some556A97680.DOCXAttorney Docket No.: 10423-2600083 embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-5172 of SEQ ID NO: 43 or SEQ ID NO: 44.

[0163] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human LAMB3 gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 45 or SEQ ID NO: 46. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 45 or SEQ ID NO: 46.

[0164] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 45 or SEQ ID NO: 46. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 45 or SEQ ID NO: 46 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, but fewer than 3519, consecutive nucleotides of SEQ ID NO: 45 or SEQ ID NO: 46. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-3516 of SEQ ID NO: 45 or SEQ ID NO: 46. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-3516 of SEQ ID NO: 45 or SEQ ID NO: 46.

[0165] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human LAMC2 gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 47 or SEQ ID NO: 48. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 47 or SEQ ID NO: 48.

[0166] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 47 or SEQ ID NO:566A97680.DOCXAttorney Docket No.: 10423-2600083 48. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 47 or SEQ ID NO: 48 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, but fewer than 3582, consecutive nucleotides of SEQ ID NO: 47 or SEQ ID NO: 48. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-3579 of SEQ ID NO: 47 or SEQ ID NO: 48. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-3579 of SEQ ID NO: 47 or SEQ ID NO: 48.Polynucleotides encoding neuromodulator proteins

[0167] In some embodiments, the present disclosure relates to a recombinant nucleic acid comprising one or more polynucleotides comprising the coding sequence of a neuromodulator gene. The coding sequence of any neuromodulator gene (including any isoform thereof) from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a Clostridium botulinum neuromodulator gene (see e.g., NCBI Gene IDs: 5185061 and 39483740), etc. Methods of identifying neuromodulator gene homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the neuromodulator genes (and / or coding sequences thereof) described herein or known in the art. In some embodiments, a polynucleotide of the present disclosure comprises a codon-optimized variant of any of the neuromodulator genes (and / or coding sequences thereof) described herein or known in the art.

[0168] In some embodiments, the present disclosure relates to one or more polynucleotides (i.e., one or more first polynucleotides and / or one or more second polynucleotides) comprising the coding sequence of a Clostridium botulinum neuromodulator gene.

[0169] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the Clostridium botulinum botA gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a 576A97680.DOCXAttorney Docket No.: 10423-2600083 sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 49 or SEQ ID NO: 50. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 49 or SEQ ID NO: 50.

[0170] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 49 or SEQ ID NO: 50. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 49 or SEQ ID NO: 50 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least about 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, but fewer than 3891, consecutive nucleotides of SEQ ID NO: 49 or SEQ ID NO: 50. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-3888 of SEQ ID NO: 49 or SEQ ID NO: 50. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-3888 of SEQ ID NO: 49 or SEQ ID NO: 50.

[0171] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the Clostridium botulinum botB gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 51 or SEQ ID NO: 52.

[0172] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 51 or SEQ ID NO: 52 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least about 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, but fewer than 586A97680.DOCXAttorney Docket No.: 10423-2600083 3876, consecutive nucleotides of SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-3873 of SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-3873 of SEQ ID NO: 51 or SEQ ID NO: 52.Polynucleotides encoding fibrillin proteins

[0173] In some embodiments, the present disclosure relates to a recombinant nucleic acid comprising one or more polynucleotides comprising the coding sequence of a fibrillin gene. The coding sequence of any fibrillin gene (including any isoform thereof) from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, human fibrillin genes (see e.g., NCBI Gene IDs: 2200, 2201, and 84467), mouse fibrillin genes (see e.g., NCBI Gene IDs: 14118 and 14119), chimpanzee fibrillin genes (see e.g., NCBI Gene IDs: 453411, 471621, and 455669), rat fibrillin genes (see e.g., NCBI Gene IDs: 83727 and 689008), rabbit fibrillin genes (see e.g., NCBI Gene IDs: 100350931, 100357126, and 100359336), etc. Methods of identifying fibrillin gene homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the fibrillin genes (and / or coding sequences thereof) described herein or known in the art. In some embodiments, a polynucleotide of the present disclosure comprises a codon-optimized variant of any of the fibrillin genes (and / or coding sequences thereof) described herein or known in the art.

[0174] In some embodiments, the present disclosure relates to one or more polynucleotides (i.e., one or more first polynucleotides and / or one or more second polynucleotides) comprising the coding sequence of a human fibrillin gene, such as a human FBN1 gene (see e.g., NCBI Gene ID: 2200), a human FBN2 gene (see e.g., NCBI Gene ID: 2201), or a human FBN3 gene (see e.g., NCBI Gene ID: 84467).Polynucleotides encoding Hyaluronan synthase proteins

[0175] In some embodiments, the present disclosure relates to a recombinant nucleic acid comprising one or more polynucleotides comprising the coding sequence of a hyaluronan 596A97680.DOCXAttorney Docket No.: 10423-2600083 synthase gene. The coding sequence of any hyaluronan synthase gene (including any isoform thereof) from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, human hyaluronan synthase genes (see e.g., NCBI Gene IDs: 3036, 3037, 3038 etc.). Methods of identifying hyaluronan synthase gene homologs / orthologs from additional species are known to one of ordinary skill in the art, including, for example, using a nucleic acid sequence alignment program such as the BLAST® blastn suite. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the hyaluronan synthase genes (and / or coding sequences thereof) described herein or known in the art.

[0176] In some embodiments, a polynucleotide of the present disclosure comprises a codon-optimized variant of the coding sequence of any of the hyaluronan synthase genes described herein or known in the art. In some embodiments, use of a codon-optimized variant of the coding sequence of a hyaluronan synthase gene increases stability and / or yield of heterologous expression (RNA and / or protein) of the encoded hyaluronan synthase protein in a target cell (such as a cell of the epidermis and / or dermis), as compared to the stability and / or yield of heterologous expression of a corresponding, non-codon-optimized, wild-type sequence. Any suitable method known in the art for performing codon optimization of a sequence for expression in one or more target cells (e.g., one or more human cells) may be used, including, for example, by the methods described by Fath et al. (PLoS One. 2011 Mar 3;6(3): el7596).

[0177] In some embodiments, the present disclosure relates to one or more polynucleotides (i.e., one or more first polynucleotides and / or one or more second polynucleotides) comprising the coding sequence of a human hyaluronan synthase gene. Any suitable human hyaluronan synthase gene (including any isoform thereof) known in the art may be encoded by a nucleic acid of the present disclosure, including, for example, a HAS1 gene (see e.g., NCBI Gene ID: 3036; SEQ ID NO: 65), aHAS2 gene (see e.g., NCBI Gene ID: 3037; SEQ ID NO: 66), aHAS3 gene (see e.g., NCBI Gene ID: 3038; SEQ ID NO: 67), etc. In some embodiments, a polynucleotide (i.e., one or more first polynucleotides and / or one or more second polynucleotides) of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 606A97680.DOCXAttorney Docket No.: 10423-2600083 98%, at least 99%, or 100% sequence identity to the sequence of any of the human hyaluronan synthase genes (and / or coding sequences thereof) described herein or known in the art.

[0178] In some embodiments, a polynucleotide (i.e., one or more first polynucleotides and / or one or more second polynucleotides) of the present disclosure comprises a codon-optimized variant of any of the human hyaluronan synthase genes described herein. In some embodiments, use of a codon-optimized variant of a human hyaluronan synthase gene increases stability and / or yield of heterologous expression (RNA and / or protein) of the human hyaluronan synthase in a target cell (such as a human keratinocyte or fibroblast), as compared to the stability and / or yield of heterologous expression of a corresponding non-codon-optimized, wild-type sequence.

[0179] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human HAS1 gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 65. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 65 or SEQ ID NO: 71.

[0180] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 65 or SEQ ID NO: 71. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 65 or SEQ ID NO: 71 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1600, at least 1700, but fewer than 1737, consecutive nucleotides of SEQ ID NO: 65 or SEQ ID NO: 71. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-1737 of SEQ ID NO: 65 or SEQ ID NO: 71. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-1737 of SEQ ID NO: 65.

[0181] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human HAS2 gene (or a codon-optimized variant thereof). In some 616A97680.DOCXAttorney Docket No.: 10423-2600083 embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 66 or SEQ ID NO: 72. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 66 or SEQ ID NO: 72.

[0182] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 66 or SEQ ID NO: 72. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 66 or SEQ ID NO: 72 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 1300, at least 1400, at least 1500, at least 1600, but fewer than 1659, consecutive nucleotides of SEQ ID NO: 66 or SEQ ID NO: 72. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-1659 of SEQ ID NO: 66 or SEQ ID NO: 72. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-1659 of SEQ ID NO: 66 or SEQ ID NO: 72.

[0183] In some embodiments, a polynucleotide of the present disclosure comprises the coding sequence of the human HAS3 gene (or a codon-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 67 or SEQ ID NO: 73. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of SEQ ID NO: 67 or SEQ ID NO: 73.

[0184] In some embodiments, a polynucleotide of the present disclosure comprises a 5’ truncation, a 3’ truncation, or a fragment of the sequence of SEQ ID NO: 67 or SEQ ID NO: 73. In some embodiments, the 5’ truncation, 3’ truncation, or fragment of the sequence of SEQ ID NO: 67 or SEQ ID NO: 73 is a polynucleotide that has at least 25, at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 250, at least 300, or at least 350, at least 400, at least 450, at least 500, at least 750, at least 1000, at least 1250, at least 626A97680.DOCXAttorney Docket No.: 10423-2600083 1300, at least 1400, at least 1500, at least 1600, but fewer than 1662, consecutive nucleotides of SEQ ID NO: 67 or SEQ ID NO: 73. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of nucleic acids 1-1662 of SEQ ID NO: 67 or SEQ ID NO: 73. In some embodiments, a polynucleotide of the present disclosure comprises the sequence of nucleic acids 1-1662 of SEQ ID NO: 67 or SEQ ID NO: 73.

[0185] In some embodiments, a polynucleotide of the present disclosure encoding one or more human hyaluronan synthase proteins (e.g., a first human hyaluronan synthase protein, a further human hyaluronan synthase protein, an additional human hyaluronan synthase protein, and / or a second human hyaluronan synthase protein) has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NOS: 65-67. In some embodiments, a polynucleotide of the present disclosure encoding one or more human hyaluronan synthase proteins (e.g., a first human hyaluronan synthase protein, a further human hyaluronan synthase protein, an additional human hyaluronan synthase protein, and / or a second human hyaluronan synthase protein) comprises a sequence selected from SEQ ID NOS: 65-67.Exemplary polynucleotides

[0186] In some embodiments, a polynucleotide of the present disclosure encoding one or more cosmetic proteins (e.g., a first cosmetic protein, a further cosmetic protein, an additional cosmetic protein, and / or a second cosmetic protein) has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NOS: 1-14, 35-52, 65-67, or 71-73. In some embodiments, a polynucleotide of the present disclosure encoding one or more cosmetic proteins (e.g., a first cosmetic protein, a further cosmetic protein, an additional cosmetic protein, and / or a second cosmetic protein) comprises a sequence selected from SEQ ID NOS: 1-14, 35-52, 65-67, or 71-73.

[0187] In some embodiments, a polynucleotide of the present disclosure encoding one or more cosmetic proteins (e.g., a first cosmetic protein, a further cosmetic protein, an additional cosmetic protein, and / or a second cosmetic protein) has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from 636A97680.DOCXAttorney Docket No.: 10423-2600083 SEQ ID NOS: 1-14, 35-38, 43-48, 65-67, or 71-73. In some embodiments, a polynucleotide of the present disclosure encoding one or more cosmetic proteins (e.g., a first cosmetic protein, a further cosmetic protein, an additional cosmetic protein, and / or a second cosmetic protein) comprises a sequence selected from SEQ ID NOS: 1-14, 35-38, 43-48, 65-67, or 71-73.

[0188] A polynucleotide of the present disclosure encoding a cosmetic protein (e.g., a human collagen protein) may further encode additional coding and non-coding sequences. Examples of additional coding and non-coding sequences may include, but are not limited to, sequences encoding additional polypeptide tags (e.g., encoded in-frame with the cosmetic protein in order to produce a fusion protein), introns (e.g., native, modified, or heterologous introns), 5’ and / or 3’ UTRs (e.g, native, modified, or heterologous 5’ and / or 3’ UTRs), and the like. Examples of suitable polypeptide tags may include, but are not limited, to any combination of purification tags, such as his-tags, flag-tags, maltose binding protein and glutathione-S-transferase tags, detection tags, such as tags that may be detected photometrically (e.g, green fluorescent protein, red fluorescent protein, etc.) and tags that have a detectable enzymatic activity (e.g., alkaline phosphatase, etc.), tags containing secretory sequences, signal sequences, leader sequences, and / or stabilizing sequences, protease cleavage sites (e.g., furin cleavage sites, TEV cleavage sites, Thrombin cleavage sites, etc.), and the like. In some embodiments, the 5’ and / or 3 ’UTRs increase the stability, localization, and / or translational efficiency of the polynucleotides. In some embodiments, the 5’ and / or 3 ’UTRs improve the level and / or duration of protein expression. In some embodiments, the 5’ and / or 3 ’UTRs include elements (e.g., one or more miRNA binding sites, etc.) that may block or reduce off-target expression (e.g., inhibiting expression in specific cell types (e.g., neuronal cells), at specific times in the cell cycle, at specific developmental stages, etc.). In some embodiments, the 5’ and / or 3 ’UTRs include elements (e.g., one or more miRNA binding sites, etc.) that may enhance cosmetic protein expression in specific cell types (such as human keratinocytes and / or fibroblasts).

[0189] In some embodiments, a polynucleotide of the present disclosure encoding a cosmetic protein (e.g., a human collagen protein) is operably linked to one or more (e.g., one or more, two or more, three or more, four or more, five or more, ten or more, etc.) regulatory sequences. The term "regulatory sequence" may include enhancers, insulators, promoters, and other expression control elements (e.g., polyadenylation signals). Any suitable enhancer(s) known in the art may be used, including, for example, enhancer sequences from mammalian genes (such as globin, elastase, albumin, a-fetoprotein, insulin and the like), enhancer sequences from a eukaryotic cell virus (such as SV40 enhancer on the late side of the replication 646A97680.DOCXAttorney Docket No.: 10423-2600083 origin (bp 100-270), the cytomegalovirus early promoter enhancer, the polyoma enhancer on the late side of the replication origin, adenovirus enhancers, and the like), and any combinations thereof. Any suitable insulator(s) known in the art may be used, including, for example, HSV chromatin boundary (CTRL / CTCF-binding / insulator) elements CTRL1 and / or CTRL2, chicken hypersensitive site 4 insulator (cHS4), human HNRPA2B1 — CBX3 ubiquitous chromatin opening element (UCOE), the scaffold / matrix attachment region (S / MAR) from the human interferon beta gene (IFNB1), and any combinations thereof. Any suitable promoter (e.g., suitable for transcription in mammalian host cells) known in the art may be used, including, for example, promoters obtained from the genomes of viruses (such as polyoma virus, fowlpox virus, adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus, Simian Virus 40 (SV40), and the like), promoters from heterologous mammalian genes (such as the actin promoter (e.g., the P-actin promoter), a ubiquitin promoter (e.g., a ubiquitin C (UbC) promoter), a phosphoglycerate kinase (PGK) promoter, an immunoglobulin promoter, from heat-shock promoters, and the like), promoters from homologous mammalian genes (e.g., native human collagen, fibronectin, elastin, lumican, vitronectin, laminin, and / or fibrillin promoters), synthetic promoters (such as the CAGG promoter), and any combinations thereof, provided such promoters are compatible with the host cells. Regulatory sequences may include those which direct constitutive expression of a nucleic acid, as well as tissue-specific regulatory and / or inducible or repressible sequences.

[0190] In some embodiments, a polynucleotide of the present disclosure encoding cosmetic protein (e.g., a human collagen protein) is operably linked to one or more heterologous promoters. In some embodiments, the one or more heterologous promoters are one or more of constitutive promoters, tissue-specific promoters, temporal promoters, spatial promoters, inducible promoters and repressible promoters. In some embodiments, the one or more heterologous promoters are one or more of the human cytomegalovirus (HCMV) immediate early promoter, the human elongation factor- 1 (EFl) promoter, the human P-actin promoter, the human UbC promoter, the human PGF promoter, the synthetic CAGG promoter, and any combinations thereof. In some embodiments, a polynucleotide of the present disclosure encoding a cosmetic protein (e.g., a human collagen protein) is operably linked to an HCMV promoter.

[0191] In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) a Collagen alpha- 1 (VII) chain polypeptide (COL7). In some embodiments, a polynucleotide of the present disclosure does not comprise 656A97680.DOCXAttorney Docket No.: 10423-2600083 the coding sequence of (e.g., a transgene encoding) a Lysyl hydroxylase 3 polypeptide (LH3). In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) a Keratin type I cytoskeletal 17 polypeptide (KRT17). In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) a transglutaminase (TGM) polypeptide (e.g., a human transglutaminase polypeptide such as a human TGM1 polypeptide and / or a human TGM5 polypeptide). In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) an antibody (e.g., a full-length antibody, an antibody fragment, etc.). In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) a Serine Protease Inhibitor Kazal-type (SPINK) polypeptide (e.g., a human SPINK polypeptide, such as a SPINK5 polypeptide). In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) a filaggrin or filaggrin 2 polypeptide (e.g., a human filaggrin or filaggrin 2 polypeptide). In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) polypeptide (e.g., a human CFTR polypeptide). In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) an ichthyosis-associated polypeptide (e.g., an ATP -binding cassette sub-family A member 12 polypeptide, a l-acylglycerol-3 -phosphate O-acyltransferase ABHD5 polypeptide, an Aldehyde dehydrogenase family 3 member A2 polypeptide, an Arachidonate 12-lipoxygenase 12R-type polypeptide, a Hydroperoxide isomerase AL0XE3 polypeptide, an AP-1 complex subunit sigma-lA polypeptide, an Arylsulfatase E polypeptide, a Caspase-14 polypeptide, a Corneodesmosin polypeptide, a Ceramide synthase 3 polypeptide, a Carbohydrate sulfotransferase 8 polypeptide, a Claudin-1 polypeptide, a Cy statin- A polypeptide, a Cytochrome P450 4F22 polypeptide, a 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase polypeptide, an Elongation of very long chain fatty acids protein 4 polypeptide, a Filaggrin polypeptide, a Filaggrin 2 polypeptide, a Gap junction beta-2 polypeptide, a Gap junction beta- 3 polypeptide, a Gap junction beta-4 polypeptide, a Gap junction beta-6 polypeptide, a 3-ketodihydrosphingosine reductase polypeptide, a Keratin, type II cytoskeletal 1 polypeptide, a Keratin, type II cytoskeletal 2 epidermal polypeptide, a Keratin, type I cytoskeletal 9 polypeptide, a Keratin, type I cytoskeletal 10 polypeptide, a Lipase member N polypeptide, a Loricrin polypeptide, a Membrane-bound transcription factor site-2 protease polypeptide, a Magnesium transporter NIPA4 polypeptide, a Sterol-4-alpha-carboxylate 3 -dehydrogenase,666A97680.DOCXAttorney Docket No.: 10423-2600083 decarboxylating polypeptide, a Peroxisomal targeting signal 2 receptor polypeptide, a D-3-phosphoglycerate dehydrogenase polypeptide, a Phytanoyl-CoA dioxygenase, peroxisomal polypeptide, Patatin-like phospholipase domain-containing protein 1 polypeptide, a Proteasome maturation protein polypeptide, a Phosphoserine aminotransferase polypeptide, a Short-chain dehydrogenase / reductase family 9C member 7 polypeptide, a Serpin B8 polypeptide, a Long-chain fatty acid transport protein 4 polypeptide, a Synaptosomal-associated protein 29 polypeptide, a Suppressor of tumorigenicity 14 protein polypeptide, a Steryl-sulfatase polypeptide, a Vacuolar protein sorting-associated protein 33B polypeptide, and a CAAX prenyl protease 1 homolog polypeptide). In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of e.g., a transgene encoding) a Collagen alpha- 1 (VII) chain polypeptide, a Lysyl hydroxylase 3 polypeptide, a Keratin type I cytoskeletal 17 polypeptide, and / or any chimeric polypeptides thereof. In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) a Collagen alpha- 1 (VII) chain polypeptide, a Lysyl hydroxylase 3 polypeptide, a Keratin type I cytoskeletal 17 polypeptide, a transglutaminase (TGM) polypeptide, a filaggrin polypeptide, an antibody, a SPINK polypeptide, a CFTR polypeptide, an ichthyosis-associated polypeptide, an Alpha- 1 -antitrypsin polypeptide, a Sodium-dependent phosphate transport protein 2B polypeptide, a Dynein heavy chain 5 axonemal polypeptide, a Dynein heavy chain 11 axonemal polypeptide, a Coiled-coil domain-containing protein 39 polypeptide, a Dynein intermediate chain 1 axonemal polypeptide, a Coiled-coil domaincontaining protein 40 polypeptide, a Coiled-coil domain containing protein 103 polypeptide, a Sperm-associated antigen 1 polypeptide, a Zinc finger MYND domain-containing protein 10 polypeptide, an Armadillo repeat containing protein 4 polypeptide, a Coiled-coil domaincontaining protein 151 polypeptide, a Dynein intermediate chain 2 axonemal polypeptide, a Radial spoke head 1 homolog polypeptide, a Coiled-coil domain-containing protein 114 polypeptide, a Radial spoke head protein 4 homolog A polypeptide, a Dynein assembly factor 1 axonemal polypeptide, a Dynein assembly factor 2 axonemal polypeptide, a Leucine-rich repeat-containing protein 6 polypeptide, a Pulmonary surfactant-associated protein B polypeptide, a Pulmonary surfactant-associated protein C polypeptide, a Homeobox protein Nkx-2.1 polypeptide, an ATP-binding cassette sub-family A member 3 polypeptide, a Cytokine receptor common subunit beta polypeptide, a Granulocyte-macrophage colony-stimulating factor receptor subunit alpha polypeptide, a Bone morphogenetic protein receptor type-2 polypeptide, a Sarcoplasmic / endoplasmic reticulum calcium ATPase 2 polypeptide, a serine / threonine-protein kinase receptor R3 polypeptide, an Endoglin polypeptide, a Mothers 676A97680.DOCXAttorney Docket No.: 10423-2600083 against decapentaplegic homolog 9 polypeptide, a Caveolin-1 polypeptide, a Potassium channel subfamily K member 3 polypeptide, an eIF-2-alpha kinase GCN2 polypeptide, a Pulmonary surfactant-associated protein A2 polypeptide, a Telomerase reverse transcriptase polypeptide, a Dyskerin polypeptide, a Regulator of telomere elongation helicase 1 polypeptide, a Poly(A)-specific ribonuclease PARN polypeptide, a TERFI -interacting nuclear factor 2 polypeptide, an H / ACA ribonucleoprotein complex non-core subunit NAF1 polypeptide, a Mucin-5B polypeptide, a Desmoplakin polypeptide, a CST complex subunit STN1 polypeptide, a Dipeptidyl peptidase 9 polypeptide, and / or any chimeric polypeptides thereof.

[0192] In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) an immunomodulatory polypeptide. In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) a cytokine polypeptide and / or a chemokine polypeptide. In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of e.g., a transgene encoding) a cytokine polypeptide. In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of e.g., a transgene encoding) an IL-1 polypeptide, an IL-2 polypeptide, an IL-7 polypeptide, an IL- 12 polypeptide, an IL- 13 polypeptide, an IL- 15 polypeptide, an IL- 17 polypeptide, an IL-18 polypeptide, an IL-28 polypeptide, an IL-32 polypeptide, an IL-33 polypeptide, an IL-34 polypeptide, a TNFa polypeptide, an IFNy polypeptide, a G-CSF polypeptide, a GM-CSF polypeptide, and / or any chimeric polypeptides thereof.

[0193] In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of e.g., a transgene encoding) a chemokine polypeptide. In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of e.g., a transgene encoding) a CXCL1 polypeptide, a CXCL2 polypeptide, a CXCL8 polypeptide, a CXCL9 polypeptide, a CXCL11 polypeptide, a CXCL16 polypeptide, a CCL2 polypeptide, a CCL3 polypeptide, a CCL4 polypeptide, a CCL5 polypeptide, a CCL11 polypeptide, and / or any chimeric polypeptides thereof.

[0194] In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of e.g., a transgene encoding) a sterile alpha motif domain-containing protein 11 polypeptide, a nephrocystin-4 polypeptide, an espin polypeptide, a nicotinamide / nicotinic acid mononucleotide adenylyltransferase 1 polypeptide, a mitofusin-2 polypeptide, an ER membrane protein complex subunit 1 polypeptide, a phospholipase A2 group V polypeptide, a dehydrodolichyl diphosphate synthase complex subunit polypeptide, a 686A97680.DOCXAttorney Docket No.: 10423-2600083 palmitoyl-protein thioesterase 1 polypeptide, an elongation of very long chain fatty acids protein 1 polypeptide, a protein O-linked-mannose beta- 1,2-N-acetylglucosaminyltransf erase 1 polypeptide, a retinoid isomerohydrolase polypeptide, a retinal-specific phospholipidtransporting ATPase ABCA4 polypeptide, a Collagen alpha- 1 (XI) polypeptide, a Guanine nucleotide-binding protein G(t) subunit alpha-2 polypeptide, a Chloride channel CLIC-like protein 1 polypeptide, a DNA damage-regulated autophagy modulator protein 2 polypeptide, an U4 / U6 small nuclear ribonucleoprotein Prp3 polypeptide, an Alpha-endosulfine polypeptide, a Semaphorin-4A polypeptide, a Cyclic AMP-dependent transcription factor ATF-6 alpha polypeptide, a Hemicentin-1 polypeptide, a Complement factor H polypeptide, a Protein crumbs homolog 1 polypeptide, an Adiponectin receptor protein 1 polypeptide, a Protein RD3 polypeptide, a Serine / threonine-protein kinase Nek2 polypeptide, a Feline leukemia virus subgroup C receptor-related protein 1 polypeptide, an Usherin polypeptide, a Serologically defined colon cancer antigen 8 polypeptide, an Olfactory receptor 2W3 polypeptide, a NBAS subunit of NRZ tethering complex polypeptide, a Cytosolic carboxypeptidase-like protein 5 polypeptide, a Zinc finger protein 513 polypeptide, an Intraflagellar transport protein 172 homolog polypeptide, a Photoreceptor cilium actin regulator polypeptide, an EGF-containing fibulin-like extracellular matrix protein 1 / TLE family member 5 polypeptide, a Protein FAM161 A polypeptide, a WD repeat-containing and planar cell polarity effector protein fritz homolog polypeptide, a Centrosome-associated protein ALMS1 polypeptide, an U5 small nuclear ribonucleoprotein 200 kDa helicase polypeptide, a Metal transporter CNNM4 polypeptide, a Cyclic nucleotide-gated cation channel alpha-3 polypeptide, a Nephrocystin-1 polypeptide, a Tyrosine-protein kinase Mer polypeptide, a Bardet-Biedl syndrome 5 protein polypeptide, a Ceramide kinase-like protein polypeptide, a Neurogenic differentiation factor 1 polypeptide, a Transmembrane protein 237 polypeptide, an Inward rectifier potassium channel 13 polypeptide, a S-arrestin polypeptide, a Secreted phosphoprotein 24 polypeptide, a CCA tRNA nucleotidyltransferase 1 polypeptide, a mitochondrial, Sodium bicarbonate cotransporter 3 polypeptide, a Leucine zipper transcription factor-like protein 1 polypeptide, a Guanine nucleotide-binding protein G(t) subunit alpha- 1 polypeptide, a Three-prime repair exonuclease 1 polypeptide, a MAP kinase-activated protein kinase 3 polypeptide, an Ataxin-7 polypeptide, a Vitamin K-dependent protein S polypeptide, an ADP-ribosylation factor-like protein 6 polypeptide, an Interphotoreceptor matrix proteoglycan 2 polypeptide, an IQ calmodulin-binding motif-containing protein 1 polypeptide, a Rhodopsin polypeptide, a Nephrocystin-3 polypeptide, a Clarin-1 polypeptide, a Probable cationic amino acid transporter / Solute carrier family 7 member 14 polypeptide, a Choline- 696A97680.DOCXAttorney Docket No.: 10423-2600083 phosphate cytidylyltransferase A polypeptide, a Centrosomal protein of 19 kDa polypeptide, a Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta polypeptide, a Wolframin, Homeobox protein HMX1 polypeptide, a Ras-related protein Rab-28 polypeptide, a Coiled-coil and C2 domain-containing protein 2 A polypeptide, a Prominin- 1 polypeptide, an Adhesion G protein-coupled receptor A3 polypeptide, a Death domain-containing protein 1 polypeptide, a WD repeat-containing protein 19 polypeptide, a cGMP-gated cation channel alpha- 1 polypeptide, a CDGSH iron-sulfur domain-containing protein 2 polypeptide, a Microsomal triglyceride transfer protein large subunit polypeptide, a Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 3 polypeptide, a Bardet-Biedl syndrome 7 protein polypeptide, a Bardet-Biedl syndrome 12 protein polypeptide, a Major facilitator superfamily domain-containing protein 8 polypeptide, a Serine / threonine-protein kinase PLK4 polypeptide, a Lecithin retinol acyltransferase polypeptide, a Toll-like receptor 3 polypeptide, a Cytochrome P4504V2 polypeptide, a Spliceosome-associated protein CWC27 homolog polypeptide, a Centrosomal protein POC5 polypeptide, a Versican core protein polypeptide, an Adhesion G-protein coupled receptor VI polypeptide, a COUP transcription factor 1 polypeptide, a Mitochondrial outer membrane protein SLC25A46 polypeptide, a Catenin alpha- 1 polypeptide, a Histi dine— tRNA ligase, cytoplasmic polypeptide, a Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha polypeptide, a Metabotropic glutamate receptor 6 polypeptide, a Serine / threonine-protein kinase MAK polypeptide, a Complement C2 polypeptide, a Complement factor B polypeptide, a Tubby-related protein 1 polypeptide, a Guanylyl cyclase-activating protein 1 polypeptide, a Guanylyl cyclase-activating protein 2 polypeptide, a Peripherin-2 polypeptide, an Interphotoreceptor matrix proteoglycan 1 polypeptide, a Protein eyes shut homolog polypeptide, a Collagen alpha- 1 (IX) chain polypeptide, a Regulating synaptic membrane exocytosis protein 1 polypeptide, a Lebercilin polypeptide, an Elongation of very long chain fatty acids protein 4 polypeptide, a PR domain zinc finger protein 13 polypeptide, a Reticulon-4-interacting protein 1, mitochondrial, polypeptide, a Jouberin polypeptide, a Peroxisomal targeting signal 2 receptor polypeptide, a CCR4-N0T transcription complex subunit 9 polypeptide, an Aryl hydrocarbon receptor polypeptide, a Kelch-like protein 7 polypeptide, a Retinitis pigmentosa 9 protein polypeptide, a Protein PTHB1 polypeptide, a Peroxisomal ATPase PEX1 polypeptide, a Tetraspanin- 12 polypeptide, an Inosine-5'-monophosphate dehydrogenase 1 polypeptide, a Short-wave-sensitive opsin 1 polypeptide, an UPF0606 protein KIAA1549 polypeptide, a Retinitis pigmentosa 1-like 1 protein polypeptide, a Disintegrin and metalloproteinase domaincontaining protein 9 polypeptide, a Heparan-alpha-glucosaminide N-acetyltransferase 706A97680.DOCXAttorney Docket No.: 10423-2600083 polypeptide, an Oxygen-regulated protein 1 polypeptide, an Alpha-tocopherol transfer protein polypeptide, a Centrosome and spindle pole-associated protein 1 polypeptide, a Dynamin-like 120 kDa protein, mitochondrial, polypeptide, a Peroxisome biogenesis factor 2 polypeptide, a Cyclic nucleotide-gated cation channel beta-3 polypeptide, a Cilia- and flagella-associated protein 418 polypeptide, a Growth / differentiation factor 6 polypeptide, a Regulating synaptic membrane exocytosis protein 2 polypeptide, a Potassium voltage-gated channel subfamily V member 2 polypeptide, an E3 ubiquitin-protein ligase Topors polypeptide, a Centrosomal protein of 78 kDa polypeptide, an Inversin polypeptide, an U4 / U6 small nuclear ribonucleoprotein Prp4 polypeptide, a Whirlin polypeptide, an E3 ubiquitin-protein ligase TRIM32 polypeptide, a Toll-like receptor 4 polypeptide, a Cytoplasmic dynein 2 intermediate chain 2 polypeptide, a Programmed cell death protein 2 polypeptide, an Exosome complex component RRP4 polypeptide, a Phosphatidylinositol polyphosphate 5-phosphatase type IV polypeptide, a Phytanoyl-CoA dioxygenase, peroxisomal, polypeptide, an Acyl-CoA-binding domain-containing protein polypeptide, a Protocadherin-15 polypeptide, a Retinol -binding protein 3 polypeptide, a DNA excision repair protein ERCC-6 polypeptide, a Hexokinase-1 polypeptide, a Cadherin-23 polypeptide, a Cadherin-related family member 1 polypeptide, a RPE-retinal G protein-coupled receptor polypeptide, a Kinesin-like protein KIF11 polypeptide, a Retinol-binding protein 4 polypeptide, a Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha polypeptide, a Paired box protein Pax-2 polypeptide, a PDZ domain-containing protein 7 polypeptide, an ADP-ribosylation factor-like protein 3 polypeptide, a BB Some-interacting protein 1 polypeptide, an Age-related maculopathy susceptibility protein 2 polypeptide, a Serine protease HTRA1 polypeptide, an Ornithine aminotransferase, mitochondrial, polypeptide, a Zinc finger protein 408 polypeptide, a Tubby protein homolog polypeptide, a Transcriptional enhancer factor TEF-1 polypeptide, a Harmonin polypeptide, a Transmembrane protein 216 polypeptide, a Bestrophin-1 polypeptide, an Isoaspartyl peptidase / L-asparaginase polypeptide, a Rod outer segment membrane protein 1 polypeptide, a Bardet-Biedl syndrome 1 protein polypeptide, a Calcium-binding protein 4 polypeptide, a Low-density lipoprotein receptor-related protein 5 polypeptide, a Calpain-5 polypeptide, an Unconventional myosin-VIIa polypeptide, a Transmembrane protein 126A polypeptide, a Frizzled-4 polypeptide, a Cytoplasmic dynein 2 light intermediate chain 1 polypeptide, a Centrosomal protein of 164 kDa polypeptide, a Complement Clq tumor necrosis factor-related protein 5 polypeptide, a Membrane frizzled-related protein polypeptide, a Voltage-dependent calcium channel subunit alpha-2 / delta-4 polypeptide, a Guanine nucleotide-binding protein G(I) / G(S) / G(T) subunit beta-3 polypeptide, a Retinal cone rhodopsin-sensitive cGMP 3', 5'- 716A97680.DOCXAttorney Docket No.: 10423-2600083 cyclic phosphodiesterase subunit gamma polypeptide, a Matrix metalloproteinase- 19 polypeptide, a Retinol dehydrogenase 5 polypeptide, a T-complex protein 1 subunit beta polypeptide, a Bardet-Biedl syndrome 10 protein polypeptide, a Centrosomal protein of 290 kDa polypeptide, a POC1 centriolar protein homolog B polypeptide, a Mevalonate kinase polypeptide, an Intraflagellar transport protein 81 homolog polypeptide, a Mitochondrial translation release factor in rescue polypeptide, an Integral membrane protein 2B polypeptide, a Retinoblastoma-associated protein polypeptide, a RCC1 and BTB domain-containing protein 1 polypeptide, a Rhodopsin kinase GRK1 polypeptide, an X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 polypeptide, a Neural retina-specific leucine zipper protein polypeptide, a Homeobox protein OTX2 polypeptide, a Retinol dehydrogenase 11 polypeptide, a Retinol dehydrogenase 12 polypeptide, a Tubulin polyglutamylase TTLL5 polypeptide, a Spermatogenesis-associated protein 7 polypeptide, a Tetratricopeptide repeat protein 8 polypeptide, a Fibulin-5 polypeptide, a Transient receptor potential cation channel subfamily M member 1 polypeptide, a Gamma-tubulin complex component 4 polypeptide, a Sodium / potassium / calcium exchanger 1 polypeptide, a Photoreceptor-specific nuclear receptor polypeptide, a Bardet-Biedl syndrome 4 protein polypeptide, a Calcium and integrin-binding family member 2 polypeptide, a Retinaldehyde-binding protein 1 polypeptide, a N-acetylglucosamine-1 -phosphotransferase subunit gamma polypeptide, an Intraflagellar transport protein 140 homolog polypeptide, a Clusterin-associated protein 1 polypeptide, an ATP-binding cassette sub-family C member 6 polypeptide, a Ketimine reductase mu-crystallin polypeptide, a Battenin polypeptide, a Zinc finger protein 423 polypeptide, a Protein fantom polypeptide, a Bardet-Biedl syndrome 2 protein polypeptide, an ADP-ribosylation factor-like protein 2-binding protein polypeptide, a Cyclic nucleotide-gated cation channel beta-1 polypeptide, a Cadherin-3 polypeptide, a Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 polypeptide, a disintegrin and metalloproteinase with thrombospondin motifs 18 polypeptide, a Solute carrier family 38 member 8 polypeptide, a Retinal guanylyl cyclase 1 polypeptide, a Pre-mRNA-processing-splicing factor 8 polypeptide, an Aryl-hydrocarbon-interacting protein-like 1 polypeptide, a Membrane-associated phosphatidylinositol transfer protein 3 polypeptide, a Protein unc-119 homolog A polypeptide, a Probable G-protein coupled receptor 179 polypeptide, a Tectonic-like complex member MKS1 polypeptide, a Carbonic anhydrase 4 polypeptide, a Regulator of G-protein signaling 9 polypeptide, an Arylsulfatase G polypeptide, a pre-mRNA splicing regulator USH1G polypeptide, a Photoreceptor disk component PRCD polypeptide, a Fascin-2 polypeptide, a Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma polypeptide, a Laminin subunit alpha-1726A97680.DOCXAttorney Docket No.: 10423-2600083 polypeptide, an AFG3-like protein 2 polypeptide, a Cone-rod homeobox protein polypeptide, a Receptor expression-enhancing protein 6 polypeptide, a Retina and anterior neural fold homeobox protein 2 polypeptide, a Complement C3 polypeptide, a Rho guanine nucleotide exchange factor 18 polypeptide, a Patatin-like phospholipase domain-containing protein 6 polypeptide, a Regulator of G-protein signaling 9-binding protein polypeptide, an Optic atrophy 3 protein polypeptide, an U4 / U6 small nuclear ribonucleoprotein Prp31 polypeptide, an Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial, polypeptide, a Pantothenate kinase 2, mitochondrial, polypeptide, a Protein jagged- 1 polypeptide, a Molecular chaperone MKKS polypeptide, a Centrosomal protein kizuna, Lysophosphatidylserine lipase ABHD12 polypeptide, a Kinesin-like protein KIF3B polypeptide, a Centrosome-associated protein CEP250 polypeptide, a Pre-mRNA-processing factor 6 polypeptide, a Cilia- and flagella-associated protein 410 polypeptide, a Dynamin-l-like protein polypeptide, a Metalloproteinase inhibitor 3 polypeptide, an Intraflagellar transport protein 27 homolog polypeptide, a Fibulin-1 polypeptide, a MIEF1 upstream open reading frame protein polypeptide, an Aconitate hydratase, mitochondrial, polypeptide, a Gamma-tubulin complex component 6 polypeptide, a Centriole and centriolar satellite protein polypeptide, a Retinoschisin, Protein XRP2 polypeptide, a Dystrophin polypeptide, an X-linked retinitis pigmentosa GTPase regulator polypeptide, a Nyctalopin polypeptide, an Xaa-Pro dipeptidase polypeptide, a Norrin polypeptide, a Voltage-dependent L-type calcium channel subunit alpha- IF polypeptide, a Phosphoglycerate kinase 1 polypeptide, a Rab proteins geranylgeranyltransferase component A 1 polypeptide, a Mitochondrial import inner membrane translocase subunit Tim8 A polypeptide, a Ribose-phosphate pyrophosphokinase 1 polypeptide, a Long-wave-sensitive opsin 1 polypeptide, a Medium-wave-sensitive opsin 1 polypeptide, a Short-wave-sensitive opsin 1 polypeptide, a Transcription factor A, mitochondrial, polypeptide, a NADH-ubiquinone oxidoreductase chain 1 polypeptide, a NADH-ubiquinone oxidoreductase chain 2 polypeptide, a NADH-ubiquinone oxidoreductase chain 3 polypeptide, a NADH-ubiquinone oxidoreductase chain 4L polypeptide, a NADH-ubiquinone oxidoreductase chain 4 polypeptide, a NADH-ubiquinone oxidoreductase chain 5 polypeptide, a NADH-ubiquinone oxidoreductase chain 6 polypeptide, an ATP synthase subunit a polypeptide, an ATP synthase protein 8 polypeptide, a Cytochrome c oxidase subunit 1 polypeptide, a Cytochrome c oxidase subunit 3 polypeptide, a Cytochrome b polypeptide, a Leucine— tRNA ligase, mitochondrial, polypeptide, a Nondiscriminating glutamyl-tRNA synthetase EARS2, mitochondrial, polypeptide, a Lysine— tRNA ligase polypeptide, a Histidine— tRNA ligase, mitochondrial, polypeptide, a Serine— tRNA ligase, mitochondrial, polypeptide, a Probable proline— tRNA 736A97680.DOCXAttorney Docket No.: 10423-2600083 ligase, mitochondrial, polypeptide, a Cyanocobalamin reductase / alkylcobalamin dealkylase polypeptide, a POU domain, class 3, transcription factor 4 polypeptide, a Ribosomal protein S6 kinase alpha-6 polypeptide, a Ciliogenesis and planar polarity effector 1 polypeptide, a Meckelin, TRAF3 -interacting protein 1 polypeptide, an Intraflagellar transport protein 74 homolog polypeptide, an S phase cyclin A-associated protein in the endoplasmic reticulum polypeptide, a Sodium channel and clathrin linker 1 polypeptide, a Protein TALPID3 polypeptide, a Tectonic-2 polypeptide, an ADP-ribosylation factor-like protein 13B polypeptide, a B9 domain-containing protein 1 polypeptide, a B9 domain-containing protein 2 polypeptide, a C2 domain-containing protein 3 polypeptide, a Centrosomal protein of 41 kDa polypeptide, a Centrosomal protein of 104 kDa polypeptide, a Centrosomal protein of 120 kDa polypeptide, an Intraflagellar transport protein 172 homolog polypeptide, a Katanin-interacting protein polypeptide, a Kinesin-like protein KIF7 polypeptide, a Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta polypeptide, a Tectonic-1 polypeptide, a Tectonic-3 polypeptide, a Transmembrane protein 107 polypeptide, a Transmembrane protein 138 polypeptide, a Transmembrane protein 231 polypeptide, a Tetratricopeptide repeat protein 2 IB polypeptide, a Nuclear receptor ROR-alpha polypeptide, a Beta-nerve growth factor polypeptide, a Solute carrier family 4 member 11 polypeptide, a Zinc finger E-box-binding homeobox 1 polypeptide, a Keratin, type II cuticular Hb3 polypeptide, a Keratin, type I cytoskeletal 12 polypeptide, a Transforming growth factor-beta-induced protein ig-h3 polypeptide, a Tumor-associated calcium signal transducer 2 polypeptide, a Carbohydrate sulfotransferase 6 polypeptide, a Gelsolin polypeptide, an UbiA prenyltransferase domaincontaining protein 1 polypeptide, a Decorin polypeptide, a 1 -phosphatidylinositol 3-phosphate 5-kinase polypeptide, a Transcription factor Ovo-like 2 polypeptide, a Grainyhead-like protein 2 homolog polypeptide, and / or any chimeric polypeptides thereof.

[0195] In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) an ATPase polypeptide. In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) a Calcium-transporting ATPase type 2C member 1 polypeptide. In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) a Sarcoplasmic / endoplasmic reticulum calcium ATPase 2 polypeptide.Cosmetic proteinsCollagen proteins746A97680.DOCXAttorney Docket No.: 10423-2600083

[0196] In some embodiments, the present disclosure relates to one or more polynucleotides encoding a full-length collagen protein or any isoforms or portions thereof. Any collagen protein from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, human collagen proteins (see e.g., UniProt accession numbers P02452, P08123, P02461, P02462, P08572, P12109, Q02388, Q9UMD9. etc.), mouse collagen proteins (see, e.g., UniProt accession numbers Pl 1087, Q01149, P08121, P02463, P08122, Q04857, Q63870, Q07563, etc.), chimpanzee collagen proteins (see e.g., UniProt accession numbers A0A2I3SM98, A0A2J8L483, H2QJ46, K7C8P4, K7C8W0, A0A2J8M8U9, H2QMJ5, H2Q2J4, etc.), rat collagen proteins (see e.g., UniProt accession numbers P02454, P02466, P13941, P02466, F1M6Q3, D3ZUL3, D3ZE04, D3ZE04, etc.), rabbit collagen proteins (see e.g., UniProt accession numbers G1T4A5, Q28668, G1T8J0, G1U9R7, G1T548, G1T380, G1T548, etc.) etc. Methods of identifying collagen protein homologs / orthologs from additional species are known to one of ordinary skill in the art, including, for example, using an amino acid sequence alignment program such as the BLAST® blastp suite or OrthoDB. In some embodiments, a collagen polypeptide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the collagen polypeptides described herein or known in the art.

[0197] In some embodiments, the present disclosure relates to one or more polynucleotides encoding a human collagen protein. Any suitable human collagen protein known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a Collagen alpha-l(I) chain polypeptide (COL1-1) (see e.g., UniProt accession number P02452; SEQ ID NO: 15), a Collagen alpha-2(I) chain polypeptide (COL 1-2) (see e.g., UniProt accession number P08123; SEQ ID NO: 16), a Collagen alpha-l(II) chain polypeptide (COL2) (see e.g., UniProt accession number P02458), a Collagen alpha-l(III) chain polypeptide (COL3) (see e.g., UniProt accession number P2461; SEQ ID NO: 17), a Collagen alpha-l(IV) chain polypeptide (COL4-1) (see e.g., UniProt accession number P02462; SEQ ID NO: 18), a Collagen alpha-2(IV) chain polypeptide (COL4-2) (see e.g., UniProt accession number P08572), a Collagen alpha-3(IV) chain polypeptide (COL4-3) (see e.g., UniProt accession number Q01955), a Collagen alpha-4(IV) chain polypeptide (COL4-4) (see e.g., UniProt accession number P53420), a Collagen alpha-5(IV) chain polypeptide (COL4-5) (see e.g., UniProt accession number 29400), a Collagen alpha-6(IV) chain polypeptide (COL4-6) (see 756A97680.DOCXAttorney Docket No.: 10423-2600083 e.g., UniProt accession number Q14031), a Collagen alpha-l(V) chain polypeptide (COL5-1) (see e.g., UniProt accession number P20908), a Collagen alpha-2(V) chain polypeptide (COL5-2) (see e.g., UniProt accession number P05997), a Collagen alpha-3(V) chain polypeptide (COL5-3) (see e.g., UniProt accession number P25940), a Collagen alpha- 1 (VI) chain polypeptide (COL6-1) (see e.g., UniProt accession number P12109; SEQ ID NO: 19), a Collagen alpha-2(VI) chain polypeptide (COL6-2) (see e.g., UniProt accession number P12110), a Collagen alpha-3(VI) chain polypeptide (COL6-3) (see e.g., UniProt accession number P12111), a Collagen alpha-4(VI) chain polypeptide (COL6-4), a Collagen alpha-5(VI) chain polypeptide (COL6-5) (see e.g., UniProt accession number A8TX70), a Collagen alpha-6(VI) chain polypeptide (COL6-6) (see e.g., UniProt accession number A6NMZ7), a Collagen alpha- 1 (VII) chain polypeptide (COL7) (see e.g., UniProt accession number Q02388; SEQ ID NO: 20), a Collagen alpha-l(VIII) chain polypeptide (COL8) (see e.g., UniProt accession number P27658), a Collagen alpha-l(IX) chain polypeptide (COL9-1) (see e.g., UniProt accession number P20849), a Collagen alpha-2(IX) chain polypeptide (COL9-2) (see e.g., UniProt accession number Q14055), a Collagen alpha-3(IX) chain polypeptide (COL9-3) (see e.g., UniProt accession number Q14050), a Collagen alpha-l(X) chain polypeptide (COLIO) (see e.g., UniProt accession number Q03692), a Collagen alpha- 1 (XI) chain polypeptide (COL11-1) (see e.g., UniProt accession number P12107), a Collagen alpha-2(XI) chain polypeptide (COL 11-2) (see e.g., UniProt accession number Pl 3942), a Collagen alpha- 1 (XII) chain polypeptide (COL 12) (see e.g., UniProt accession number Q99715), a Collagen alpha-l(XIII) chain polypeptide (COL13) (see e.g., UniProt accession number Q5TAT6), a Collagen alpha-l(XIV) chain polypeptide (COL14) (see e.g., UniProt accession number Q05707), a Collagen alpha- 1 (XV) chain polypeptide (COL 15) (see e.g., UniProt accession number P39059), a Collagen alpha-l(XVI) chain polypeptide (COL16) (see e.g., UniProt accession number Q07092), a Collagen alpha-l(XVII) chain polypeptide (COL17) (see e.g., UniProt accession number Q9UMD9; SEQ ID NO: 21), a Collagen alpha- 1 (XVIII) chain polypeptide (COL 18) (see e.g., UniProt accession number P39060), a Collagen alpha- 1 (XIX) chain polypeptide (COL19) (see e.g., UniProt accession number Q14993), a Collagen alpha-l(XX) chain polypeptide (COL20) (see e.g., UniProt accession number Q9P218), a Collagen alpha-l(XXI) chain polypeptide (COL21) (see e.g., UniProt accession number Q96P44), a Collagen alpha-l(XXII) chain polypeptide (COL22) (see e.g., UniProt accession number Q8NFW1), a Collagen alpha- 1 (XXIII) chain polypeptide (COL23) (see e.g., UniProt accession number Q86Y22), a Collagen alpha-l(XXIV) chain polypeptide (COL24) (see e.g., UniProt accession number Q17RW2), a Collagen alpha- 1 (XXV) chain polypeptide (COL25) (see e.g., UniProt 766A97680.DOCXAttorney Docket No.: 10423-2600083 accession number Q9BXS0), a Collagen alpha- 1 (XXVI) chain polypeptide (COL26) (see e.g., UniProt accession number Q96A83), a Collagen alpha- 1 (XXVII) chain polypeptide (COL27) see e.g., UniProt accession number Q8IZC6), a Collagen alpha- 1 (XXVIII) chain polypeptide (COL28) (see e.g., UniProt accession number Q2UY09), etc. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence encoding any of the human collagen polypeptides described herein or known in the art. Methods of identifying additional human collagen or collagen-like polypeptide homologs / orthologs are known to one of ordinary skill in the art, including, for example, using an amino acid sequence alignment program such as the BLAST® blastp suite or OrthoDB.

[0198] In some embodiments, a polynucleotide of the present disclosure encodes a human COL1-1 protein. In some embodiments, a polynucleotide encoding a COL1-1 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 15. In some embodiments, a polynucleotide encoding a human COL 1-1 protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 15.

[0199] In some embodiments, a polynucleotide encoding a COL1-1 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 15. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, at least 1200, at least 1300, at least 1400, but fewer than 1464, consecutive amino acids of SEQ ID NO: 15.

[0200] In some embodiments, a polynucleotide of the present disclosure encodes a human COL1-2 protein. In some embodiments, a polynucleotide encoding a COL1-2 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 776A97680.DOCXAttorney Docket No.: 10423-2600083 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 16. In some embodiments, a polynucleotide encoding a human COL 1-2 protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 16.

[0201] In some embodiments, a polynucleotide encoding a COL 1-2 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 16. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, at least 1200, at least 1300, but fewer than 1366, consecutive amino acids of SEQ ID NO: 16.

[0202] In some embodiments, a polynucleotide of the present disclosure encodes a human COL3 protein. In some embodiments, a polynucleotide encoding a COL3 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 17. In some embodiments, a polynucleotide encoding a human COL3 protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 17.

[0203] In some embodiments, a polynucleotide encoding a COL3 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 17. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, at least 1200, at least 1300, at least 1400, but fewer than 1466, consecutive amino acids of SEQ ID NO: 17.

[0204] In some embodiments, a polynucleotide of the present disclosure encodes a human COL4-1 protein. In some embodiments, a polynucleotide encoding a COL4-1 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO:786A97680.DOCXAttorney Docket No.: 10423-2600083 18. In some embodiments, a polynucleotide encoding a human COL4-1 protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 18.

[0205] In some embodiments, a polynucleotide encoding a COL4-1 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 18. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, at least 1200, at least 1300, at least 1400, at least 1500, at least 1600, but fewer than 1669, consecutive amino acids of SEQ ID NO: 18.

[0206] In some embodiments, a polynucleotide of the present disclosure encodes a human COL6-1 protein. In some embodiments, a polynucleotide encoding a COL6-1 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 19. In some embodiments, a polynucleotide encoding a human COL6-1 protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 19.

[0207] In some embodiments, a polynucleotide encoding a COL6-1 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 19. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, but fewer than 1028, consecutive amino acids of SEQ ID NO: 19.

[0208] In some embodiments, a polynucleotide of the present disclosure encodes a human COL7 protein. In some embodiments, a polynucleotide encoding a COL7 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 20. In some embodiments, a polynucleotide encoding a human COL7 protein is a 796A97680.DOCXAttorney Docket No.: 10423-2600083 polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 20.

[0209] In some embodiments, a polynucleotide encoding a COL7 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 20. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, at least 1200, at least 1300, at least 1400, at least 1500, at least 1600, at least 1700, at least 1800, at least 1900, at least 2000, at least 2100, at least 2200, at least 2300, at least 2400, at least 2500, at least 2600, at least 2700, at least 2800, at least 2900, but fewer than 2944, consecutive amino acids of SEQ ID NO: 20.

[0210] In some embodiments, a polynucleotide of the present disclosure encodes a human COL 17 protein. In some embodiments, a polynucleotide encoding a COL 17 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 21. In some embodiments, a polynucleotide encoding a human COL17 protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 21.

[0211] In some embodiments, a polynucleotide encoding a COL17 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 21. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, at least 1200, at least 1300, at least 1400, but fewer than 1497, consecutive amino acids of SEQ ID NO: 21.

[0212] In some embodiments, one or more human collagen proteins of the present disclosure (e.g., a first human collagen protein, a further human collagen protein, an additional human collagen protein, and / or a second human collagen protein) comprise an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 806A97680.DOCXAttorney Docket No.: 10423-2600083 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments, one or more human collagen proteins of the present disclosure (e.g., a first human collagen protein, a further human collagen protein, an additional human collagen protein, and / or a second human collagen protein) comprise a sequence selected from SEQ ID NOS: 15-21.

[0213] In some embodiments, one or more human collagen proteins of the present disclosure (e.g., a first human collagen protein, a further human collagen protein, an additional human collagen protein, and / or a second human collagen protein) comprise an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-17. In some embodiments, one or more human collagen proteins of the present disclosure (e.g., a first human collagen protein, a further human collagen protein, an additional human collagen protein, and / or a second human collagen protein) comprise a sequence selected from SEQ ID NOS: 15-17.Fibronectin proteins

[0214] In some embodiments, the present disclosure relates to one or more polynucleotides encoding a full-length fibronectin protein or any isoforms or portions thereof. Any fibronectin protein from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a human fibronectin protein (see e.g., UniProt accession number P02751), a mouse fibronectin protein (see, e.g., UniProt accession number Pl 1276), a chimpanzee fibronectin protein (see e.g., UniProt accession number Pl 1276), a rat fibronectin protein (see e.g., UniProt accession number P04937), a rabbit fibronectin protein (see e.g., UniProt accession number P04937), etc. Methods of identifying fibronectin protein homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, a fibronectin protein of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the fibronectin proteins described herein or known in the art.

[0215] In some embodiments, a polynucleotide of the present disclosure encodes a human fibronectin protein. In some embodiments, a polynucleotide encoding a human fibronectin protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 816A97680.DOCXAttorney Docket No.: 10423-2600083 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 53. In some embodiments, a polynucleotide encoding a human fibronectin protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 53.

[0216] In some embodiments, a polynucleotide encoding a human fibronectin protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 53. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, at least 1200, at least 1300, at least 1400, at least 1500, at least 1600, at least 1700, at least 1800, at least 1900, at least 2000, at least 2100, at least 2200, at least 2300, at least 2400, but fewer than 2477, consecutive amino acids of SEQ ID NO: 53.Elastin and associated proteins

[0217] Elastic fibers in the extracellular matrix give elastic properties to the tissue. The elastic fibers generally contain two morphologically distinct components - the mature elastin fibers, and the micro-fibrills which mainly contain fibrillin and are associated with further proteins such as the micro-fibrills associated glycoproteins (MAGPs), fibulines, and the elastin-micro-fibrills-interface localized proteins (EMILIN). Elastin and its soluble precursor tropoelastin belong to the major structural proteins of the body.

[0218] In some embodiments, the present disclosure relates to one or more polynucleotides encoding an elastin or elastin-associated protein, including a tropoelastin, a fibrillin, a micro-fibrills associated glycoprotein, a fibuline, or an elastin-micro-fibrills-interface localized protein. In some embodiments, the present disclosure relates to one or more polynucleotides encoding a full-length elastin protein or any isoforms or portions thereof. Any elastin protein from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a human elastin protein (see e.g., UniProt accession number P15502), a mouse elastin protein (see, e.g., UniProt accession number Pl 5502), a chimpanzee elastin protein (see e.g., UniProt accession number H2QUQ6), a rat elastin protein (see e.g., UniProt accession number Q99372), etc. Methods of identifying elastin protein homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, an elastin protein of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%,826A97680.DOCXAttorney Docket No.: 10423-2600083 at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the elastin proteins described herein or known in the art.

[0219] In some embodiments, a polynucleotide of the present disclosure encodes a human elastin protein. In some embodiments, a polynucleotide encoding a human elastin protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 54. In some embodiments, a polynucleotide encoding a human elastin protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 54.

[0220] In some embodiments, a polynucleotide encoding a human elastin protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 54. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, but fewer than 786, consecutive amino acids of SEQ ID NO: 54.Lumican proteins

[0221] In some embodiments, the present disclosure relates to one or more polynucleotides encoding a full-length lumican protein or any isoforms or portions thereof. Any lumican protein from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a human lumican protein (see e.g., UniProt accession number P51884), a mouse lumican protein (see, e.g., UniProt accession number P51885), a chimpanzee lumican protein (see e.g., UniProt accession number H2Q6L3), a rat lumican protein (see e.g., UniProt accession number H2Q6L3), a rabbit lumican protein (see e.g., UniProt accession number 046379), etc. Methods of identifying lumican protein homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, a lumican protein of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the lumican proteins described herein or known in the art.836A97680.DOCXAttorney Docket No.: 10423-2600083

[0222] In some embodiments, a polynucleotide of the present disclosure encodes a human lumican protein. In some embodiments, a polynucleotide encoding a human lumican protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 55. In some embodiments, a polynucleotide encoding a human lumican protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 55.

[0223] In some embodiments, a polynucleotide encoding a human lumican protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 55. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, but fewer than 338, consecutive amino acids of SEQ ID NO: 55.Vitronectin and vitronectin receptor proteins

[0224] In some embodiments, the present disclosure relates to one or more polynucleotides encoding a full-length vitronectin or vitronectin receptor protein or any isoforms or portions thereof. Any vitronectin or vitronectin receptor protein from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a human vitronectin or vitronectin receptor protein (see e.g., UniProt accession numbers P04004 and P06756), a mouse vitronectin or vitronectin receptor protein (see, e.g., UniProt accession numbers P29788 and P43406), a chimpanzee vitronectin or vitronectin receptor protein (see e.g., UniProt accession numbers H2QCH3 and H2R6C3), a rat vitronectin or vitronectin receptor protein (see e.g., UniProt accession number Q7TQ11), a rabbit vitronectin or vitronectin receptor protein (see e.g., UniProt accession number P22458), etc. Methods of identifying vitronectin or vitronectin receptor protein homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, a vitronectin or vitronectin receptor protein of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the vitronectin or vitronectin receptor proteins described herein or known in the art.846A97680.DOCXAttorney Docket No.: 10423-2600083

[0225] In some embodiments, a polynucleotide of the present disclosure encodes a human vitronectin protein. In some embodiments, a polynucleotide encoding a human vitronectin protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 56. In some embodiments, a polynucleotide encoding a human vitronectin protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 56.

[0226] In some embodiments, a polynucleotide encoding a human vitronectin protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 56. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, but fewer than 478, consecutive amino acids of SEQ ID NO: 56.Laminin proteins

[0227] In some embodiments, the present disclosure relates to one or more polynucleotides encoding a full-length laminin protein or any isoforms or portions thereof. Any laminin protein from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a human laminin protein (see e.g., UniProt accession numbers P25391, P24043, Q16787, Q16363, 015230, P07942, P55268, Q13751, Pl 1047, Q13753, and Q9Y6N6), a mouse laminin protein (see e.g., UniProt accession numbers Q61789, Q61087, and Q61092), a chimpanzee laminin protein (see e.g., UniProt accession numbers H2QEC7, H2R041, and H2Q0R2), a rat laminin protein (see e.g., UniProt accession numbers D3ZN05, F1LPI5, and F1LRH4), a rabbit laminin protein (see e.g., UniProt accession numbers G1SY40 and A0A0B5JSH0), etc. Methods of identifying laminin protein homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, a laminin protein of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the laminin proteins described herein or known in the art.

[0228] In some embodiments, a polynucleotide of the present disclosure encodes a human laminin protein, such as a human Laminin subunit alpha-1 (LamAl) polypeptide (see e.g.,856A97680.DOCXAttorney Docket No.: 10423-2600083 UniProt accession number P25391), a human Laminin subunit alpha-2 (LamA2) polypeptide (see e.g., UniProt accession number P24043), a human Laminin subunit alpha-3 (LamA3) polypeptide (see e.g., UniProt accession number Q16787), a human Laminin subunit alpha-4 (LamA4) polypeptide (see e.g., UniProt accession number Q16363), a human Laminin subunit alpha-5 (LamA5) polypeptide (see e.g., UniProt accession number 015230), a human Laminin subunit beta-1 (LamBl) polypeptide (see e.g., UniProt accession number P07942), a human Laminin subunit beta-2 (LamB2) polypeptide (see e.g., UniProt accession number P55268), a human Laminin subunit beta-3 (LamB3) polypeptide (see e.g., UniProt accession number Q13751), a human Laminin subunit gamma-1 (LamCl) polypeptide (see e.g., UniProt accession number Pl 1047), a human Laminin subunit gamma-2 (LamC2) polypeptide (see e.g., UniProt accession number Q13753), a human Laminin subunit gamma-3 (LamC3) polypeptide (see e.g., UniProt accession number Q9Y6N6), etc.

[0229] In some embodiments, a polynucleotide of the present disclosure encodes a human LamA3 polypeptide. In some embodiments, a polynucleotide encoding a human LamA3 polypeptide is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 57. In some embodiments, a polynucleotide encoding a human LamA3 polypeptide is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 57.

[0230] In some embodiments, a polynucleotide encoding a human LamA3 polypeptide is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 57. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2250, at least 2500, at least 2750, at least 3000, at least 3250, but fewer than 3333, consecutive amino acids of SEQ ID NO: 57.

[0231] In some embodiments, a polynucleotide of the present disclosure encodes a human LamB3 polypeptide. In some embodiments, a polynucleotide encoding a human LamB3 polypeptide is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 866A97680.DOCXAttorney Docket No.: 10423-2600083 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 58. In some embodiments, a polynucleotide encoding a human LamB3 polypeptide is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 58.

[0232] In some embodiments, a polynucleotide encoding a LamB3 polypeptide is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 58. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, but fewer than 1172, consecutive amino acids of SEQ ID NO: 58.

[0233] In some embodiments, a polynucleotide of the present disclosure encodes a human LamC2 polypeptide. In some embodiments, a polynucleotide encoding a human LamC2 polypeptide is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 59. In some embodiments, a polynucleotide encoding a human LamC2 polypeptide is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 59.

[0234] In some embodiments, a polynucleotide encoding a LamC2 polypeptide is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 59. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, but fewer than 1193, consecutive amino acids of SEQ ID NO: 59.Neuromodulator proteins

[0235] In some embodiments, the present disclosure relates to one or more polynucleotides encoding a full-length neuromodulator protein or any isoforms or portions thereof. Any neuromodulator protein from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a Clostridium botulinum protein (see e.g., UniProt accession numbers P0DPI0, Q45894, P0DPI1, P10844, andBHNP5), etc. Methods of identifying neuromodulator protein homologs / orthologs from additional 876A97680.DOCXAttorney Docket No.: 10423-2600083 species are known to one of ordinary skill in the art. In some embodiments, a neuromodulator protein of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the neuromodulator proteins described herein or known in the art.

[0236] In some embodiments, a polynucleotide of the present disclosure encodes a Clostridium botulinum neuromodulator protein.

[0237] In some embodiments, a polynucleotide of the present disclosure encodes a Clostridium botulinum neurotoxin type A protein In some embodiments, a polynucleotide encoding a Clostridium botulinum neurotoxin type A protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 60. In some embodiments, a polynucleotide encoding a Clostridium botulinum neurotoxin type A protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 60. In some embodiments, a Clostridium botulinum neurotoxin type A protein of the present disclosure comprises an alanine to valine mutation at a position corresponding to position 27 of SEQ ID NO: 60.

[0238] In some embodiments, a polynucleotide encoding a Clostridium botulinum neurotoxin type A protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 60. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, at least 1200, but fewer than 1296, consecutive amino acids of SEQ ID NO: 60.

[0239] In some embodiments, a polynucleotide of the present disclosure encodes a Clostridium botulinum neurotoxin type B protein In some embodiments, a polynucleotide encoding a Clostridium botulinum neurotoxin type B protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%,886A97680.DOCXAttorney Docket No.: 10423-2600083 or 100% sequence identity to the sequence of SEQ ID NO: 61. In some embodiments, a polynucleotide encoding a Clostridium botulinum neurotoxin type B protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 61.

[0240] In some embodiments, a polynucleotide encoding a Clostridium botulinum neurotoxin type B protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 61. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, at least 1200, but fewer than 1291, consecutive amino acids of SEQ ID NO: 61.Fibrillin proteins

[0241] In some embodiments, the present disclosure relates to one or more polynucleotides encoding a full-length fibrillin protein or any isoforms or portions thereof. Any fibrillin protein from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a human fibrillin protein (see e.g., UniProt accession numbers P35555, P35556, and Q75N90), a mouse fibrillin protein (see, e.g., UniProt accession numbers Q61554 and Q61555), a chimpanzee fibrillin protein (see e.g., UniProt accession numbers A0A2I3RTE4 and K7CZX0 ), a rat fibrillin protein (see e.g., UniProt accession number G3V9M6 and F1M5Q4), a rabbit fibrillin protein (see e.g., UniProt accession number G1SKM2, G1SUS5, and G1T1H4), etc. Methods of identifying fibrillin protein homologs / orthologs from additional species are known to one of ordinary skill in the art. In some embodiments, a fibrillin protein of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the fibrillin proteins described herein or known in the art.

[0242] In some embodiments, a polynucleotide of the present disclosure encodes a human fibrillin protein.

[0243] In some embodiments, a polynucleotide of the present disclosure encodes a human flbrillin-1 protein. In some embodiments, a polynucleotide encoding a human flbrillin-1 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at 896A97680.DOCXAttorney Docket No.: 10423-2600083 least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 62. In some embodiments, a polynucleotide encoding a human flbrillin-1 protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 62.

[0244] In some embodiments, a polynucleotide encoding a human fibrillin- 1 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 62. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2250, at least 2500, at least 2750, but fewer than 2871, consecutive amino acids of SEQ ID NO: 62.

[0245] In some embodiments, a polynucleotide of the present disclosure encodes a human flbrillin-2 protein. In some embodiments, a polynucleotide encoding a human flbrillin-2 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 63. In some embodiments, a polynucleotide encoding a human flbrillin-2 protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 63.

[0246] In some embodiments, a polynucleotide encoding a human flbrillin-2 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 63. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2250, at least 2500, at least 2750, but fewer than 2912, consecutive amino acids of SEQ ID NO: 63.

[0247] In some embodiments, a polynucleotide of the present disclosure encodes a human flbrillin-3 protein. In some embodiments, a polynucleotide encoding a human flbrillin-3 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at 906A97680.DOCXAttorney Docket No.: 10423-2600083 least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 64. In some embodiments, a polynucleotide encoding a human flbrillin-3 protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 64.

[0248] In some embodiments, a polynucleotide encoding a human flbrillin-3 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 64. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 750, at least 1000, at least 1250, at least 1500, at least 1750, at least 2000, at least 2250, at least 2500, at least 2750, but fewer than 2809, consecutive amino acids of SEQ ID NO: 64.Hyaluronan Synthase proteins

[0249] In some embodiments, the present disclosure relates to one or more polynucleotides encoding a full-length hyaluronan synthase protein or any isoforms or portions thereof. Any hyaluronan synthase protein from any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, human hyaluronan synthase proteins (see e.g., UniProt accession numbers Q92839, Q92819, 000219, etc.). Methods of identifying hyaluronan synthase protein homologs / orthologs from additional species are known to one of ordinary skill in the art, including, for example, using an amino acid sequence alignment program such as the BLAST® blastp suite or OrthoDB. In some embodiments, a hyaluronan synthase polypeptide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of any of the hyaluronan synthase polypeptides described herein or known in the art.

[0250] In some embodiments, the present disclosure relates to one or more polynucleotides encoding a human hyaluronan synthase protein. Any suitable human hyaluronan synthase protein known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a Hyaluronan synthase 1 (see e.g., UniProt accession number Q92839; SEQ ID NO: 68), a Hyaluronan synthase 2 (see e.g., UniProt accession number Q92819; SEQ ID NO: 69), a Hyaluronan synthase 3 (see e.g., UniProt accession number 000219; SEQ ID NO: 70), etc. In some embodiments, a polynucleotide of the present disclosure comprises a sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 916A97680.DOCXAttorney Docket No.: 10423-2600083 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence encoding any of the human hyaluronan synthase polypeptides described herein or known in the art. Methods of identifying additional human hyaluronan synthase or hyaluronan synthase-like polypeptide homologs / orthologs are known to one of ordinary skill in the art, including, for example, using an amino acid sequence alignment program such as the BLAST® blastp suite or OrthoDB.

[0251] In some embodiments, a polynucleotide of the present disclosure encodes a human Hyaluronan synthase 1 protein. In some embodiments, a polynucleotide encoding a Hyaluronan synthase 1 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 68. In some embodiments, a polynucleotide encoding a human Hyaluronan synthase 1 protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 68.

[0252] In some embodiments, a polynucleotide encoding a Hyaluronan synthase 1 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 68. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, but fewer than 578, consecutive amino acids of SEQ ID NO: 68.

[0253] In some embodiments, a polynucleotide of the present disclosure encodes a human Hyaluronan synthase 2 protein. In some embodiments, a polynucleotide encoding a Hyaluronan synthase 2 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 69. In some embodiments, a polynucleotide encoding a human Hyaluronan synthase 2 protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 69.

[0254] In some embodiments, a polynucleotide encoding a Hyaluronan synthase 2 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 69. N-terminal truncations, C-terminal 926A97680.DOCXAttorney Docket No.: 10423-2600083 truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, but fewer than 552, consecutive amino acids of SEQ ID NO: 69.

[0255] In some embodiments, a polynucleotide of the present disclosure encodes a human Hyaluronan synthase 3 protein. In some embodiments, a polynucleotide encoding a Hyaluronan synthase 3 protein is a polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the sequence of SEQ ID NO: 70. In some embodiments, a polynucleotide encoding a human Hyaluronan synthase 3 protein is a polynucleotide that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 70.

[0256] In some embodiments, a polynucleotide encoding a Hyaluronan synthase 3 protein is a polynucleotide that encodes an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence of SEQ ID NO: 70. N-terminal truncations, C-terminal truncations, or fragments may comprise at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, but fewer than 553, consecutive amino acids of SEQ ID NO: 70.

[0257] In some embodiments, one or more human hyaluronan synthase proteins of the present disclosure (e.g., a first human hyaluronan synthase protein, a further human hyaluronan synthase protein, an additional human hyaluronan synthase protein, and / or a second human hyaluronan synthase protein) comprise an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 68-70. In some embodiments, one or more human hyaluronan synthase proteins of the present disclosure (e.g., a first human hyaluronan synthase protein, a further human hyaluronan synthase protein, an additional human hyaluronan synthase protein, and / or a second human hyaluronan synthase protein) comprise a sequence selected from SEQ ID NOS: 68-70.Exemplary cosmetic polypeptides

[0258] In some embodiments, one or more cosmetic proteins of the present disclosure (e.g., a first cosmetic protein, a further cosmetic protein, an additional cosmetic protein, and / or a second cosmetic protein) comprise an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 936A97680.DOCXAttorney Docket No.: 10423-2600083 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21, 53-64, or 68-70. In some embodiments, one or more cosmetic proteins of the present disclosure (e.g., a first cosmetic protein, a further cosmetic protein, an additional cosmetic protein, and / or a second cosmetic protein) comprises a sequence selected from SEQ ID NOS: 15-21, 53-64, or 68-70.

[0259] In some embodiments, one or more cosmetic proteins of the present disclosure (e.g., a first cosmetic protein, a further cosmetic protein, an additional cosmetic protein, and / or a second cosmetic protein) comprise an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 15-21, 53-54, or 57-59. In some embodiments, one or more cosmetic proteins of the present disclosure (e.g., a first cosmetic protein, a further cosmetic protein, an additional cosmetic protein, and / or a second cosmetic protein) comprise a sequence selected from SEQ ID NOS: 15-21, 53-54, or 57-59.First polynucleotides

[0260] In some embodiments, the present disclosure relates to a recombinant nucleic acid comprising a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein. The first cosmetic protein may be any of the cosmetic proteins described herein or known in the art, including, for example a collagen protein, a fibronectin, an elastin, a lumican, a vitronectin / vitronectin receptor, a laminin, a neuromodulator, a fibrillin, a hyaluronan synthase, etc. In some embodiments, the first cosmetic protein is a structural extracellular matrix protein (e.g., a collagen, elastin, fibronectin, laminin, fibrillin, etc.). In some embodiments, the first cosmetic protein is a collagen, elastin, fibronectin, laminin protein, or a hyaluronan synthase (e.g., a human collagen, elastin, fibronectin, laminin, or hyaluronan synthase protein).

[0261] In some embodiments, a recombinant nucleic acid of the present disclosure comprises one copy of the first polynucleotide. In some embodiments, a recombinant nucleic acid of the present disclosure comprises two or more (e.g., two or more, three or more, four or more, five or more, ten or more, etc.) copies of the first polynucleotide. In some embodiments, a recombinant nucleic acid of the present disclosure comprises two copies of the first polynucleotide.

[0262] In some embodiments, the first cosmetic protein is a first human collagen protein. The first human collagen protein may be any of the human collagen proteins described herein or known in the art. In some embodiments, the first human collagen protein is selected from 946A97680.DOCXAttorney Docket No.: 10423-2600083 C0L1-1, C0L1-2, C0L2, C0L3, C0L4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, C0L5-1, COL5-2, COL5-3, C0L6-1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, C0L7, C0L8, C0L9-1, COL9-2, COL9-3, COL 10, COL11-1, COL 11-2, COL 12, COL13, COL 14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, or COL28. In some embodiments, the first human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1, COL7, or COL17. In some embodiments, the first human collagen protein is COL1-1. In some embodiments, the first human collagen protein is COL1-2. In some embodiments, the first human collagen protein is COL3. In some embodiments, the first human collagen protein is COL4-1. In some embodiments, the first human collagen protein is COL4-2. In some embodiments, the first human collagen protein is COL6-1. In some embodiments, the first human collagen protein is COL7. In some embodiments, the first human collagen protein is not COL7. In some embodiments, the first human collagen protein is COL17.

[0263] In some embodiments, the first cosmetic protein is a first human hyaluronan synthase protein. The first human hyaluronan synthase protein may be any of the human hyaluronan synthase proteins described herein or known in the art. In some embodiments, the first human hyaluronan synthase protein is selected from hyaluronan synthase 1, hyaluronan synthase 2, or hyaluronan synthase 3. In some embodiments, the first human hyaluronan synthase protein is hyaluronan synthase 1. In some embodiments, the first human hyaluronan synthase protein is hyaluronan synthase 2. In some embodiments, the first human hyaluronan synthase protein is hyaluronan synthase 3.

[0264] In some embodiments, the first polypeptide consists essentially of the first cosmetic protein. In some embodiments, the first polypeptide consists of the first cosmetic protein. In some embodiments, the first polypeptide is the first cosmetic protein.Chimeric polypeptides

[0265] In some embodiments, the first polypeptide is a chimeric polypeptide comprising the first cosmetic protein. In some embodiments, the first polypeptide is a chimeric polypeptide comprising the first cosmetic protein and a further cosmetic protein. In some embodiments, the chimeric polypeptide comprises a linker polypeptide linking the first cosmetic protein and the further cosmetic protein. In some embodiments, the chimeric polypeptide comprises, from n-terminus to c-terminus, the first cosmetic protein-the linker polypeptide-the further cosmetic protein. The first and / or further cosmetic proteins may be any of the cosmetic proteins described herein or known in the art, including, for example a collagen protein, a fibronectin, an elastin, a lumican, a vitronectin / vitronectin receptor, a laminin, a neuromodulator, a fibrillin,956A97680.DOCXAttorney Docket No.: 10423-2600083 a hyaluronan synthase, etc. In some embodiments, the first and / or further cosmetic protein is a structural extracellular matrix protein (e.g., a collagen, elastin, fibronectin, laminin, fibrillin, etc.). In some embodiments, the first and / or further cosmetic protein is a collagen, elastin, fibronectin, laminin, or hyaluronan synthase protein (e.g., a human collagen, elastin, fibronectin, laminin, or hyaluronan synthase protein). In some embodiments, the first and further cosmetic proteins are the same. In some embodiments, the first and further cosmetic proteins are different.

[0266] In some embodiments, the linker polypeptide is a cleavable linker polypeptide. Any cleavable linker polypeptide known in the art may be used in the chimeric polypeptides of the present disclosure, including, for example, a T2A linker, a P2A linker, a E2A linker, and F2A linker, etc. In some embodiments, the linker polypeptide is a T2A linker polypeptide. An exemplary nucleic acid sequence encoding a T2A linker polypeptide is provided as SEQ ID NO: 24. An exemplary amino acid sequence of a T2A linker polypeptide is provided as SEQ ID NO: 28. In some embodiments, the linker polypeptide is a P2A linker polypeptide. An exemplary nucleic acid sequence encoding a P2A linker polypeptide is provided as SEQ ID NO: 25. An exemplary amino acid sequence of a P2A linker polypeptide is provided as SEQ ID NO: 29. In some embodiments, the linker polypeptide is an E2A linker polypeptide. An exemplary nucleic acid sequence encoding an E2A linker polypeptide is provided as SEQ ID NO: 26. An exemplary amino acid sequence of an E2A linker polypeptide is provided as SEQ ID NO: 30. In some embodiments, the linker polypeptide is an F2A linker polypeptide. An exemplary nucleic acid sequence encoding an F2A linker polypeptide is provided as SEQ ID NO: 27. An exemplary amino acid sequence of an F2A linker polypeptide is provided as SEQ ID NO: 31.

[0267] In some embodiments, the linker polypeptide comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from SEQ ID NOS: 28-31. In some embodiments, the linker polypeptide comprises a sequence selected from SEQ ID NOS: 28-31.

[0268] In some embodiments, the first cosmetic protein is a first collagen protein (e.g., a first human collagen protein), and the further cosmetic protein is a further collagen protein (e.g., a further human collagen protein). An exemplary nucleic acid sequence encoding a chimeric polypeptide comprising a first human collagen protein, a linker polypeptide, and a further human collagen protein is provided as SEQ ID NO: 32.966A97680.DOCXAttorney Docket No.: 10423-2600083

[0269] In some embodiments, the first cosmetic protein is a first human collagen protein, and the further cosmetic protein is a further human collagen protein. The further human collagen protein may be any of the human collagen proteins described herein or known in the art. In some embodiments, the further human collagen protein is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6-1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COLIO, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, or COL28. In some embodiments, the further human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1, COL7, or COL17. In some embodiments, the further human collagen protein is COL1-1. In some embodiments, the further human collagen protein is COL1-2. In some embodiments, the further human collagen protein is COL3. In some embodiments, the further human collagen protein is COL4-1. In some embodiments, the further human collagen protein is COL4-2. In some embodiments, the further human collagen protein is COL6-1. In some embodiments, the further human collagen protein is COL7. In some embodiments, the further human collagen protein is not COL7. In some embodiments, the further human collagen protein is COL17. In some embodiments, the first human collagen protein and the further human collagen protein are the same. In some embodiments, the first human collagen protein and the further human collagen protein are different.

[0270] In some embodiments, the first human collagen protein is COL1-1, and the further human collagen protein is selected from COL1-2, COL3, COL4-1, COL4-2, COL6-1, COL7, or COL17. In some embodiments, the first human collagen protein is COL1-1, and the further human collagen protein is COL1-2. In some embodiments, the first human collagen protein is COL 1-1, and the further human collagen protein is COL3.

[0271] In some embodiments, the first human collagen protein is COL1-2, and the further human collagen protein is COL1-1, COL3, COL4-1, COL4-2, COL6-1, COL7, or COL17. In some embodiments, the first human collagen protein is COL 1-2, and the further human collagen protein is COL1-1.

[0272] In some embodiments, the first human collagen protein is COL3, and the further human collagen protein is selected from COL1-1, COL1-2, COL4-1, COL4-2, COL6-1, COL7, or COL17.

[0273] In some embodiments, the first human collagen protein is COL4-1, and the further human collagen protein is COL1-1, COL1-2, COL3, COL4-2, COL6-1, COL7, or COL17. In 976A97680.DOCXAttorney Docket No.: 10423-2600083 some embodiments, the first human collagen protein is COL4-1, and the further human collagen protein is COL4-2.

[0274] In some embodiments, the first human collagen protein is COL6-1, and the further human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL7, or COL17.

[0275] In some embodiments, the first human collagen protein is COL7, and the further human collagen protein is COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1, or COL17.

[0276] In some embodiments, the first human collagen protein is COL17, and the further human collagen protein is COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1, or COL7.

[0277] In some embodiments, the first cosmetic protein is a first laminin protein (e.g., a first human laminin protein), and the further cosmetic protein is a further laminin protein (e.g., a further human laminin protein). In some embodiments, the first cosmetic protein is a first human laminin protein, and the further cosmetic protein is a further human laminin protein. The further human laminin protein may be any of the human laminin proteins described herein or known in the art. In some embodiments, the first human laminin protein is a human LamA3 polypeptide and the further human laminin protein is a human LamB3 polypeptide. In some embodiments, the first human laminin protein is a human LamA3 polypeptide and the further human laminin protein is a human LamC2 polypeptide. In some embodiments, the first human laminin protein is a human LamB3 polypeptide and the further human laminin protein is a human LamC2 polypeptide.

[0278] In some embodiments, the first polynucleotide encodes a monocistronic mRNA. In some embodiments, the monocistronic mRNA comprises an open reading frame (ORF) encoding the first polypeptide.

[0279] In some embodiments, the first polynucleotide encodes a polycistronic mRNA. In some embodiments, the polycistronic mRNA comprises an open reading frame (ORF) encoding the first polypeptide.Polycistronic mRNA

[0280] In some embodiments, the first polynucleotide encodes a polycistronic mRNA. In some embodiments, the polycistronic mRNA comprises an open reading frame (ORF) encoding the first polypeptide. In some embodiments, the first polynucleotide encodes a polycistronic mRNA comprising: 1) a first open reading frame (ORF) encoding the first polypeptide, and 2) a second open reading frame (ORF) encoding an additional cosmetic protein. In some embodiments, the polycistronic mRNA further comprises an internal ribosomal entry site (IRES) separating the first ORF and the second ORF. In some 986A97680.DOCXAttorney Docket No.: 10423-2600083 embodiments, the polycistronic mRNA comprises, from 5’ to 3’, the first ORF encoding the first polypeptide-the IRES-the second ORF encoding the additional cosmetic protein. The first polypeptide may be any of the first polypeptides described herein. The additional cosmetic protein may be any of the cosmetic proteins described herein or known in the art, including, for example a collagen protein, a fibronectin, an elastin, a lumican, a vitronectin / vitronectin receptor, a laminin, a neuromodulator, a fibrillin, etc. In some embodiments, the additional cosmetic protein is a structural extracellular matrix protein (e.g., a collagen, elastin, fibronectin, laminin, fibrillin, etc.}. In some embodiments, the additional cosmetic protein is a collagen, elastin, fibronectin, or laminin protein (e.g., a human collagen, elastin, fibronectin, or laminin protein).

[0281] Any suitable IRES known in the art may be used in the polycistronic mRNAs of the present disclosure, including, for example, a virally-derived IRES e.g. an IRES derived from a poliovirus, rhinovirus, encephalomyocarditis virus (EMCV), foot-and-mouth disease virus, hepatitis C virus, classic swine fever virus, rous sarcoma virus, human immunodeficiency virus, cricket paralysis virus, Kaposi’s sarcoma-associated herpesvirus, etc. , a cellular mRNA-derived IRES (e.g. an IRES derived from growth factor mRNAs, such as fibroblast growth factor 2, platelet-derived growth factor B, and vascular endothelial growth factor; an IRES derived from transcription factor mRNAs, such as antennapedia, ultrabithorax, and NF-KB repressing factor; an IRES derived from oncogene mRNAs, such as c-myc, pim-1, and protein kinase p58PITSLRE, etc.}, a synthetic IRES (e.g., a CP148 IRES), and others see e.g., Mokrejs et al. (2007) A Bioinformatical Approach to the Analysis of Viral and Cellular Internal Ribosome Entry Sites. Columbus F editors. New Messenger RNA Research Communications. Hauppauge, NY: Nova Science Publishers; pp. 133-166). In some embodiments, the IRES is a CP148 IRES. An exemplary nucleic acid sequence encoding a CP148 IRES is provided as SEQ ID NO: 22. In some embodiments, the IRES is an EMCV IRES. An exemplary nucleic acid sequence encoding an EMCV IRES is provided as SEQ ID NO: 23.

[0282] In some embodiments, the nucleic acid sequence encoding the IRES comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments, the nucleic acid sequence encoding the IRES comprises the sequence of SEQ ID NO: 22 or SEQ ID NO: 23.

[0283] In some embodiments, the first polypeptide is a first collagen protein (e.g., a first human collagen protein), and the additional cosmetic protein is an additional collagen protein 996A97680.DOCXAttorney Docket No.: 10423-2600083 (e.g., an additional human collagen protein). An exemplary nucleic acid encoding a polycistronic mRNA comprising a first ORF, an IRES, and second ORF is provided as SEQ ID NO: 33 or SEQ ID NO: 34. The additional human collagen protein may be any of the human collagen proteins described herein. In some embodiments, the additional human collagen protein is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6-1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COLIO, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, or COL28. In some embodiments, the additional human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1, COL7, or COL17. In some embodiments, the additional human collagen protein is COL1-1. In some embodiments, the additional human collagen protein is COL1-2. In some embodiments, the additional human collagen protein is COL3. In some embodiments, the additional human collagen protein is COL4-1. In some embodiments, the additional human collagen protein is COL4-2. In some embodiments, the additional human collagen protein is COL6-1. In some embodiments, the additional human collagen protein is COL7. In some embodiments, the additional human collagen protein is not COL7. In some embodiments, the additional human collagen protein is COL17. In some embodiments, the first human collagen protein and the additional human collagen protein are the same. In some embodiments, the first human collagen protein and the additional human collagen protein are different.

[0284] In some embodiments, the first human collagen protein is COL1-1, and the additional human collagen protein is selected from COL1-2, COL3, COL4-1, COL4-2, COL6-1, COL7, or COL17. In some embodiments, the first human collagen protein is COL1-1, and the additional human collagen protein is COL1-2. In some embodiments, the first human collagen protein is COL1-1, and the additional human collagen protein is COL3.

[0285] In some embodiments, the first human collagen protein is COL1-2, and the additional human collagen protein is selected from COL1-1, COL3, COL4-1, COL4-2, COL6-1, COL7, or COL17. In some embodiments, the first human collagen protein is COL1-2, and the additional human collagen protein is COL1-1.

[0286] In some embodiments, the first human collagen protein is COL3, and the additional human collagen protein is selected from COL1-1, COL1-2, COL4-1, COL4-2, COL6-1, COL7, or COL17.

[0287] In some embodiments, the first human collagen protein is COL4-1, and the additional human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-2, COL6- 1006A97680.DOCXAttorney Docket No.: 10423-2600083 1, C0L7, or COL17. In some embodiments, the first human collagen protein is COL4-1, and the additional human collagen protein is COL4-2.

[0288] In some embodiments, the first human collagen protein is COL6-1, and the additional human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4- 2, COL7, or COL17.

[0289] In some embodiments, the first human collagen protein is COL7, and the additional human collagen protein is selected from COL 1-1, COL 1-2, COL3, COL4-1, COL4-2, COL6- 1, or COL17.

[0290] In some embodiments, the first human collagen protein is COL 17, and the additional human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4- 2, COL6-1, or COL7.

[0291] In some embodiments, the first polypeptide is a first collagen protein (e.g., a first human collagen protein), and the additional cosmetic protein is an additional collagen protein (e.g., an additional human collagen protein).

[0292] In some embodiments, the first polypeptide is a first laminin protein (e.g., a first human laminin protein), and the additional cosmetic protein is an additional laminin protein (e.g., an additional human laminin protein). In some embodiments, the first polypeptide is a first human laminin protein, and the additional cosmetic protein is an additional human laminin protein. The additional human laminin protein may be any of the human laminin proteins described herein or known in the art. In some embodiments, the first human laminin protein is a human LamA3 polypeptide and the additional human laminin protein is a human LamB3 polypeptide. In some embodiments, the first human laminin protein is a human LamA3 polypeptide and the additional human laminin protein is a human LamC2 polypeptide. In some embodiments, the first human laminin protein is a human LamB3 polypeptide and the additional human laminin protein is a human LamC2 polypeptide.Second polynucleotides

[0293] In some embodiments, the present disclosure relates to a recombinant nucleic acid further comprising a second polynucleotide encoding a second cosmetic protein. The second cosmetic protein may be any of the cosmetic proteins described herein or known in the art, including, for example a collagen protein, a fibronectin, an elastin, a lumican, a vitronectin / vitronectin receptor, a laminin, a neuromodulator, a fibrillin, etc. In some embodiments, the second cosmetic protein is a structural extracellular matrix protein (e.g., a collagen, elastin, fibronectin, laminin, fibrillin, etc.). In some embodiments, the second cosmetic protein is a collagen, elastin, fibronectin, or laminin protein (e.g., a human collagen,1016A97680.DOCXAttorney Docket No.: 10423-2600083 elastin, fibronectin, or laminin protein). In some embodiments, the first and second cosmetic proteins are the same. In some embodiments, the first and second cosmetic proteins are different. In some embodiments, the recombinant nucleic acid comprises one copy of the second polynucleotide. In some embodiments, the recombinant nucleic acid comprises two or more (e.g., two or more, three or more, four or more, five or more, ten or more, etc.) copies of the second polynucleotide. In some embodiments, the recombinant nucleic acid comprises two copies of the second polynucleotide.

[0294] In some embodiments, the second cosmetic protein is a collagen protein. In some embodiments, the second cosmetic protein is a second human collagen protein. The second human collagen protein may be any of the human collagen proteins described herein. In some embodiments, the second human collagen protein is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL4-6, COL5-1, COL5-2, COL5-3, COL6-1, COL6-2, COL6-3, COL6-4, COL6-5, COL6-6, COL7, COL8, COL9-1, COL9-2, COL9-3, COLIO, COL11-1, COL11-2, COL12, COL13, COL14, COL15, COL16, COL17, COL18, COL19, COL20, COL21, COL22, COL23, COL24, COL25, COL26, COL27, or COL28. In some embodiments, the second human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL6-1, COL7, or COL17. In some embodiments, the second human collagen protein is COL1-1. In some embodiments, the second human collagen protein is COL1-2. In some embodiments, the second human collagen protein is COL3. In some embodiments, the second human collagen protein is COL4-1. In some embodiments, the second human collagen protein is COL4-2. In some embodiments, the second human collagen protein is COL6-1. In some embodiments, the second human collagen protein is COL7. In some embodiments, the second human collagen protein is not COL7. In some embodiments, the second human collagen protein is COL17.

[0295] In some embodiments, the first polynucleotide encodes a first collagen protein and the second polynucleotide encodes a second collagen protein. In some embodiments, the first polynucleotide encodes a first human collagen protein and the second polynucleotide encodes a second human collagen protein. In some embodiments, the first human collagen protein (encoded by the first polynucleotide) and the second human collagen protein (encoded by the second polynucleotide) are the same. In some embodiments, the first human collagen protein (encoded by the first polynucleotide) and the second human collagen protein (encoded by the second polynucleotide) are different.

[0296] In some embodiments, the first human collagen protein is COL1-1, and the second human collagen protein is selected from COL1-2, COL3, COL4-1, COL4-2, COL6-1, COL7,1026A97680.DOCXAttorney Docket No.: 10423-2600083 or COL17. In some embodiments, the first huma...

Claims

Attorney Docket No.: 10423-2600083CLAIMSWhat is claimed is:

1. Use of a composition in the manufacture of a medicament for treating a subject’s decollete, the composition comprising a herpes virus comprising a recombinant herpes virus genome, wherein the recombinant herpes virus genome comprises a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein.

2. A method of enhancing, increasing, augmenting, and / or supplementing the levels of one or more dermal extracellular matrix proteins in a subject’s decollete, the method comprising administering to the subject’s decollete an effective amount of a composition, the composition comprising a herpes virus comprising a recombinant herpes virus genome, wherein the recombinant herpes virus genome comprises a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein.

3. A method of improving the condition, quality, and / or appearance of a subject’s decollete, the method comprising administering to the subject’s decollete an effective amount of a composition, the composition comprising a herpes virus comprising a recombinant herpes virus genome, wherein the recombinant herpes virus genome comprises a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein.

4. The method of claim 3, wherein the composition is administered to one or more sites of sun damage or other UV exposure, rough texture, skin sagging, wrinkles, or any combinations thereof.

5. A method of reducing the appearance of one or more superficial depressions of a subject’s decollete, the method comprising administering to the subject’s decollete an effective amount of a composition, the composition comprising a herpes virus comprising a recombinant herpes virus genome, wherein the recombinant herpes virus genome comprises a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein.

6. The method of claim 5, wherein the one or more superficial depressions of the subject’s decollete are selected from the group consisting of scars, poikiloderma of Civatte, hyperpigmentation, upper chest lines, chest wrinkles, neck lines, neck wrinkles, platysma bands, and any combinations thereof.

7. A method of increasing and / or improving at least one of texture, smoothness, elasticity, pigmentation, thinness, hydration, or tension of a subject’s decollete, the method comprising1766A97680.DOCXAttorney Docket No.: 10423-2600083 administering to the subject’s decollete an effective amount of a composition, the composition comprising a herpes virus comprising a recombinant herpes virus genome, wherein the recombinant herpes virus genome comprises a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein.

8. The method of any one of claims 3-7, wherein the subject’s decollete is aging skin.

9. The method of any one of claims 3-8, wherein the subject’s decollete has been damaged due to exposure to ultraviolet light.

10. The method of any one of claims 3-9, wherein the subject’s decollete is wrinkled.

11. A method of diminishing one or more dermatological signs of aging of a subject’s decollete, the method comprising administering to the subject’s decollete an effective amount of a composition, the composition comprising a herpes virus comprising a recombinant herpes virus genome, wherein the recombinant herpes virus genome comprises a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein.

12. The method of claim 11, wherein the diminishing of one or more dermatological signs of aging of the subject’s decollete is indicated by the: (a) treatment, reduction, and / or prevention of fine lines and / or wrinkles; (b) reduction of skin pore size; (c) improvement in skin thickness, plumpness, and / or tautness; (d) improvement in skin smoothness, suppleness, and / or softness; (e) improvement in skin tone, radiance, and / or clarity; (f) improvement in procollagen and / or collagen production; (g) improvement in skin texture and or promotion of retexturization; (h) improvement in appearance of skin contours; (i) restoration of skin luster and / or brightness; (j) improvement of skin appearance decreased by aging and / or menopause; (k) improvement in skin moisturization; (1) increase in skin elasticity and / or resiliency; (m) treatment, reduction, and / or prevention or skin sagging; (n) improvement in skin firmness; (o) reduction of pigment spots, mottled skin, and / or scars; (p) improvement of optical properties of skin by light diffraction or reflection; (q) improvement in skin pigmentation; (r) improvement in skin thinness; (s) improvement in skin hydration; or (t) any combinations thereof.

13. The method of any one of claims 2-12, wherein the subject is a human.

14. The method of any one of claims 2-13, wherein the composition is administered topically, transdermally, subcutaneously, epicutaneously, intradermally, orally, sublingually, buccally, rectally, vaginally, intraurethrally, intravenously, intraarterially, intramuscularly, intraosseously, intracardially, intraperitoneally, transmucosally, intravitreally, subretinally,1776A97680.DOCXAttorney Docket No.: 10423-2600083 intraarticularly, peri-articularly, locally, via injection, via superficial injection, via micro-depot injection, or via inhalation to the subject.

15. The method of any one of claims 2-14, wherein the composition is administered intradermally to the subject.

16. The method of any one of claims 2-14, wherein the composition is administered by injection.

17. The method of any one of claims 2-16, wherein the composition is administered by superficial injection.

18. The method of any one of claims 2-17, wherein the composition is administered by micro-depot injection.

19. The method of any one of claims 2-18, further comprising applying a grid to the subject’s decollete to mark one or more injection sites.

20. The method of claim 19, wherein the one or more injection sites are spaced about 0.5 cm, about 1.0 cm, about 1.5 cm, about 2.0 cm, about 2.5 cm, about 3.0 cm, about 3.5 cm, about 4.0 cm, about 4.5 cm, or about 5.0 cm apart from each other.

21. The method of claim 19 or claim 20, wherein administering the composition comprises one or more injections at each of the one or more injections sites.

22. The method of any one of claims 19-21, wherein the one or more injections comprises a volume in a range from about 0.01 mL to about 2.00 mL.

23. The method of any one of claims 2-22, wherein administering the composition occurs at least once per day for up to 60 days.

24. The method of any one of claims 2-23, wherein administering the composition comprises administering the virus at a concentration in a range from about IxlO4PFU / mL to about IxlO12PFU / mL.

25. The method of any one of claims 2-24, further comprising administering to the subj ect’ s decollete an agent selected from the group consisting of an anesthetic agent, an anti-microbial agent, a vasoconstrictor, an anti-thrombotic agent, an anti-coagulation agent, a dispersion agent, an anti-dispersion agent, a penetration enhancer, a steroid, a tranquilizer, a muscle relaxant, an anti-diarrhea agent, and a combination thereof.1786A97680.DOCXAttorney Docket No.: 10423-2600083 26. The method of any one of claims 2-25, wherein the recombinant herpes virus genome comprises two or more copies of the first polynucleotide.

27. The method of any one of claims 2-26, wherein the recombinant herpes virus genome is replication competent.

28. The method of any one of claims 2-26, wherein the recombinant herpes virus genome is replication defective.

29. The method of any one of claims 2-28, 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.

30. The method of any one of claims 2-29, wherein the recombinant herpes virus genome is a recombinant herpes simplex virus genome.

31. The method of claim 30, wherein the recombinant herpes simplex virus genome is a recombinant herpes simplex virus type 1 (HSV-1) genome, a recombinant herpes simplex virus type 2 (HSV-2) genome, or any derivatives thereof.

32. The method of claim 30 or claim 31, wherein the recombinant herpes simplex virus genome is a recombinant herpes simplex virus type 1 (HSV-1) genome.

33. The method of any one of claims 30-32, wherein the recombinant herpes simplex virus genome comprises an inactivating mutation.

34. The method of claim 33, wherein the inactivating mutation is in a herpes simplex virus gene.

35. The method of claim 34, wherein the inactivating mutation is a deletion of the coding sequence of the herpes simplex virus gene.

36. The method of claim 34 or claim 35, wherein the herpes simplex virus gene is selected from the group consisting of Infected Cell Protein (ICP) 0, ICP4, ICP22, ICP27, ICP47, thymidine kinase (tk), Long Unique Region (UL) 41, and UL55.

37. The method of claim 36, wherein the recombinant herpes simplex virus genome comprises an inactivating mutation in one or both copies of the ICP4 gene.1796A97680.DOCXAttorney Docket No.: 10423-2600083 38. The method of claim 36 or claim 37, wherein the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP22 gene.

39. The method of any one of claims 36-38, wherein the recombinant herpes simplex virus genome comprises an inactivating mutation in the UL41 gene.

40. The method of any one of claims 36-39, wherein the recombinant herpes simplex virus genome comprises an inactivating mutation in one or both copies of the ICPO gene.

41. The method of any one of claims 36-40, wherein the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP27 gene.

42. The method of any one of claims 30-41, wherein the recombinant herpes simplex virus genome comprises the first polynucleotide within one or both of the ICP4 viral gene loci.

43. The method of any one of claims 2-42, wherein the first cosmetic protein is selected from the group consisting of a first collagen protein, a first fibronectin protein, a first elastin protein, a first lumican protein, a first vitronectin protein, a first vitronectin receptor protein, a first laminin protein, a first neuromodulator protein, a first fibrillin protein, and a first hyaluronan synthase protein.

44. The method of any one of claims 2-43, wherein the first cosmetic protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 15-21, 53-64, and 68-70.

45. The method of any one of claims 2-44, wherein the first cosmetic protein is a structural extracellular matrix protein.

46. The method of any one of claims 43-45, wherein the first collagen protein is a human collagen protein.

47. The method of any one of claims 43-46, wherein the first collagen protein is selected from the group consisting of Collagen alpha-l(I) chain polypeptide (COL1-1), Collagen alpha-2(1) chain polypeptide (COL 1-2), a Collagen alpha- 1(11) chain polypeptide (COL2), a Collagen alpha-l(III) chain polypeptide (COL3), a Collagen alpha-l(IV) chain polypeptide (COL4-1), a Collagen alpha-2(IV) chain polypeptide (COL4-2), a Collagen alpha-3 (IV) chain polypeptide (COL4-3), a Collagen alpha-4(IV) chain polypeptide (COL4-4), a Collagen alpha-5(IV) chain polypeptide (COL4-5), a Collagen alpha-6(IV) chain polypeptide (COL4-6), a Collagen alpha-1806A97680.DOCXAttorney Docket No.: 10423-2600083 1(V) chain polypeptide (C0L5-1), a Collagen alpha-2(V) chain polypeptide (COL5-2), a Collagen alpha-3(V) chain polypeptide (COL5-3), a Collagen alpha-l(VI) chain polypeptide (C0L6-1), a Collagen alpha-2(VI) chain polypeptide (COL6-2), a Collagen alpha-3 (VI) chain polypeptide (COL6-3), a Collagen alpha-4(VI) chain polypeptide (COL6-4), a Collagen alpha-5(VI) chain polypeptide (COL6-5), a Collagen alpha-6(VI) chain polypeptide (COL6-6), a Collagen alpha- 1 (VIII) chain polypeptide (C0L8), a Collagen alpha- 1 (IX) chain polypeptide (C0L9-1), a Collagen alpha-2(IX) chain polypeptide (COL9-2), a Collagen alpha-3 (IX) chain polypeptide (COL9-3), a Collagen alpha-l(X) chain polypeptide (COLIO), a Collagen alpha-1(XI) chain polypeptide (C0L11-1), a Collagen alpha-2(XI) chain polypeptide (C0L11-2), a Collagen alpha- 1 (XII) chain polypeptide (COL 12), a Collagen alpha- 1 (XIII) chain polypeptide (C0L13), a Collagen alpha-l(XIV) chain polypeptide (C0L14), a Collagen alpha-l(XV) chain polypeptide (COL 15), a Collagen alpha- 1 (XVI) chain polypeptide (COL 16), a Collagen alpha-l(XVII) chain polypeptide (COL 17), a Collagen alpha- 1 (XVIII) chain polypeptide (COL 18), a Collagen alpha- 1 (XIX) chain polypeptide (COL 19), a Collagen alpha- 1 (XX) chain polypeptide (COL20), a Collagen alpha- 1 (XXI) chain polypeptide (COL21), a Collagen alpha-l(XXII) chain polypeptide (COL22), a Collagen alpha- 1 (XXIII) chain polypeptide (COL23), a Collagen alpha- 1 (XXIV) chain polypeptide (COL24), a Collagen alpha- 1 (XXV) chain polypeptide (COL25), a Collagen alpha- 1 (XXVI) chain polypeptide (COL26), a Collagen alpha- 1 (XXVII) chain polypeptide (COL27), and a Collagen alpha- 1 (XXVIII) chain polypeptide (COL28).

48. The method of any one of claims 43-47, wherein the first collagen protein is selected from the group consisting of COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1, and COL 17.

49. The method of any one of claims 43-48, wherein the first human collagen protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 17.

50. The method of any one of claims 2-44, wherein the first cosmetic protein is selected from the group consisting of hyaluronan synthase 1, hyaluronan synthase2, and hyaluronan synthase 3.

51. The method of claim 50, wherein the first hyaluronan synthase protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least1816A97680.DOCXAttorney Docket No.: 10423-2600083 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 69.

52. The method of any one of claims 2-51, wherein the first cosmetic protein is not a Collagen alpha- 1 (VII) chain polypeptide (COL7).

53. The method of any one of claims 2-52, wherein the first polypeptide consists essentially of or consists of the first cosmetic protein.

54. The method of any one of claims 2-52, wherein the first polypeptide comprises: (a) the first cosmetic protein; (b) a further cosmetic protein; and (c) a linker polypeptide linking (a) to (b).

55. The method of claim 54, wherein the linker polypeptide is a cleavable linker polypeptide.

56. The method of claim 54 or claim 55, wherein the linker polypeptide comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 28-31.

57. The method of any one of claims 54-56, wherein the first cosmetic protein and the further cosmetic protein are different.

58. The method of any one of claims 2-57, wherein the first polynucleotide encodes a polycistronic mRNA comprising: (a) a first open reading frame (ORF) encoding the first polypeptide; (b) a second ORF encoding an additional cosmetic protein; and (c) an internal ribosomal entry site (IRES) separating (a) and (b).

59. The method of claim 58, wherein the nucleic acid sequence encoding the IRES has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence selected from SEQ ID NO: 22 or SEQ ID NO: 23.

60. The method of claim 58 or claim 59, wherein the first cosmetic protein and the additional cosmetic protein are different.

61. The method of any one of claims 2-60, wherein the recombinant herpes virus genome further comprises a second polynucleotide encoding a second cosmetic protein.1826A97680.DOCXAttorney Docket No.: 10423-2600083 62. The method of claim 61, wherein the first and second cosmetic proteins are different.

63. The method of claim 61, wherein the first and second cosmetic proteins are the same.

64. The method of any one of claims 2-63, wherein the recombinant herpes virus genome has reduced cytotoxicity when introduced into a target cell, as compared to a corresponding wild-type herpes virus genome.

65. The method of claim 64, wherein the target cell is a cell of the epidermis and / or dermis.

66. The method of claim 64 or claim 65, wherein the target cell is a human cell.

67. The method of any one of claims 64-66, wherein the target cell is a fibroblast.

68. The method of any one of claims 2-67, wherein the herpes virus is replication competent.

69. The method of any one of claims 2-67, wherein the herpes virus is replication defective.

70. The method of any one of claims 2-69, wherein the herpes virus has reduced cytotoxicity as compared to a corresponding wild-type herpes virus.

71. The method of any one of claims 2-70, wherein the 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.

72. The method of any one of claims 2-71, wherein the herpes virus is a herpes simplex virus.

73. The method of claim 72, wherein the herpes simplex virus is a herpes simplex virus type 1 (HSV-1), a herpes simplex virus type 2 (HSV-2), or any derivatives thereof.

74. The method of any one of claims 2-73, wherein the composition is sterile.

75. The method of any one of claims 2-74, wherein the composition is suitable for topical, transdermal, subcutaneous, intradermal, oral, intranasal, intratracheal, sublingual, buccal, rectal, vaginal, urethral, inhaled, intravenous, intraarterial, intramuscular, intracardiac, intraosseous, intraperitoneal, transmucosal, intravitreal, subretinal, intraarticular, periarticular, local, or epicutaneous administration.

76. The method of any one of claims 2-75, wherein the composition is suitable for intradermal administration.1836A97680.DOCXAttorney Docket No.: 10423-2600083 77. The method of any one of claims 2-76, wherein the composition is suitable for superficial injection.

78. The method of any one of claims 2-77, wherein the composition is suitable for microdepot injection.

79. The method of any one of claims 2-78, wherein the composition is a cosmetic composition.

80. The method of any one of claims 2-79, wherein the composition is a skin care product.1846A97680.DOCX

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