Uses of a cosmetic composition

Description

[001] This application claims priority of the Patent Application Provisional US 62 / 663,476, filed on April 27, 2018, which is incorporated herein by reference in its entirety. PRESENTATION OF A SEQUENCE LISTING IN AN ASCII TEXT FILE

[002] The contents of the following submission in ASCII text file are incorporated here by reference in their entirety: a machine-readable form (CRF) of the Sequence Listing (filename: 761342000640SEQLIST.txt, registration date: April 26, 2019, size: 437 KB) FIELD OF THE INVENTION

[003] This 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); to viruses comprising recombinant nucleic acids; to compositions (e.g., cosmetic formulations) comprising recombinant nucleic acids and / or viruses; to methods of their use; and to articles of manufacture or kits thereof. BACKGROUND

[004] The skin, like all organs in the human body, undergoes sequential and often cumulative changes over time. Skin aging occurs as a result of several factors, including changes inherent to the skin, the effects of gravity and facial muscles acting on the skin, loss or displacement of soft tissue, and loss of tissue elasticity. Interestingly, the “aged” phenotype of the skin can be accelerated by environmental factors, most notably, chronic exposure to Petition 870260060403, dated 06 / 19 / 2026, page 14 / 300 / 237 ultraviolet radiation (e.g., from the sun). Clinically, the aged skin phenotype can be described as wrinkled, sagging, and / or generally less elastic and resilient than its youthful counterpart, although there are variations within this phenotype between natural chronological aging and photoaging.

[005] The dermal extracellular matrix (ECM) comprises the majority of the skin and confers strength and resilience. Collagen, an important component of connective tissue that provides support to the skin, decreases with aging. In aged skin, collagen fibrils exhibit high levels of degradation and fragmentation and are replaced by dermal fibroblasts at decreasing rates. These bundles of degraded and fragmented collagen become looser and lose strength (disrupting the structural organization of the dermal ECM), and inextricably lead to an “aged” manifestation of the skin.

[006] Various skincare products have been developed to improve the appearance of human skin. Wrinkles and skin folds are commonly treated with dermal and subdermal injections of aesthetic facial fillers; however, this superficial approach does not address the underlying structural changes of skin aging, in particular, collagen damage or loss. Thus, there is a clear need for alternative strategies to supplement, strengthen, or replace dermal components of the ECM (e.g., human collagen) in individuals who wish to combat or reverse the physiological effects of skin aging.

[007] All references cited herein, including patent applications, patent publications, and NCBI / UniProtKB / Swiss-Prot accession numbers, are incorporated herein by reference in their entirety, as if each individual reference were specifically and individually indicated for incorporation by reference. BRIEF SUMMARY Petition 870260060403, dated 06 / 19 / 2026, p. 15 / 300 / 237

[008] In order to meet these and other needs, 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., wrinkle treatment) are provided in this document. The present inventors have demonstrated that the recombinant attenuated viruses described herein were capable of 1) effectively transducing human epidermal / dermal cells and 2) successfully expressing the encoded exogenous human collagen (mRNA and protein), where the protein could then localize to the appropriate region in skin-equivalent organotypic cultures (see, for example, Example 2).Furthermore, the present inventors have shown that the viruses described in this document can be successfully administered both topically and intradermally without significant cytotoxicity to the host cell, allowing the human collagen expressed from these viruses to localize to the appropriate region of the dermal ECM after in vivo administration without observable skin damage (see, for example, Examples 3 and 7).Furthermore, the present inventors have demonstrated that several different HSV backbones can be used to construct viruses that express human collagens (see, for example, Example 2), that multiple strategies can be employed to successfully express more than one human collagen protein from a single recombinant genome (see, for example, Example 5), and that the candidate viruses can successfully express human collagen proteins in multiple relevant in vitro and in vivo models of chronological or UV-induced skin aging (see, for example, Examples 6 and 7). In addition, the present inventors have demonstrated that the viruses described herein can be successfully engineered to express other cosmetic proteins (e.g., human laminins) both in vitro and in vivo, where these proteins localize to the appropriate region of the dermal ECM (see, for example, Example 8). Petition 870260060403, dated 06 / 19 / 2026, page 16 / 300 / 237, wishing to be limited by theory, the data described herein provide strong evidence that the recombinant nucleic acids and / or viruses of the present disclosure may constitute a novel means of delivering cosmetic proteins (e.g., human collagen proteins such as Human Collagen 1 and Human Collagen 3) and, in particular, of supplementing or replacing natural human dermal ECM proteins in aesthetic applications (e.g., to reduce the appearance of photo-induced aging or wrinkles).

[009] Therefore, certain aspects of the present disclosure relate to a recombinant herpesvirus genome comprising a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein. In some embodiments, the recombinant herpesvirus genome comprises two or more copies of the first polynucleotide. In some embodiments, the recombinant herpesvirus genome is replication-competent. In some embodiments, the recombinant herpesvirus genome is replication-defective.In some embodiments that can be combined with any of the previous embodiments, the recombinant herpesvirus 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 can be combined with any of the previous embodiments, the recombinant herpesvirus genome 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, a recombinant herpes simplex virus type 2 (HSV-2) genome, or any derivatives thereof. Petition 870260060403, dated 06 / 19 / 2026, p. 17 / 300 / 237

[0010] In some embodiments, the recombinant herpes simplex virus genome is a recombinant herpes simplex virus type 1 (HSV1) genome. In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation. In some embodiments that can be combined with any of the previous embodiments, the inactivation mutation is in a herpes simplex virus gene. In some embodiments, the inactivation 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), Single Long Region (UL) 41, and UL55.In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in one or both copies of the ICP4 gene. In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP22 gene. In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the UL41 gene. In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in one or both copies of the ICP0 gene.In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP27 gene. In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the UL55 gene. In some embodiments that can be combined with any of the embodiments. Petition 870260060403, dated 06 / 19 / 2026, p. 18 / 300 / 237 above, the genome of the recombinant herpes simplex virus comprises an inactivation mutation in the Junta region. In some embodiments, the genome of the recombinant herpes simplex virus comprises a deletion of the Junta region. In some embodiments that can be combined with any of the above embodiments, the genome of the recombinant herpes simplex virus comprises the first polynucleotide in one or both loci of the viral gene ICP4.

[0011] In some embodiments that can be combined with any of the previous 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, and a first fibrillin protein. In some embodiments that can be combined with any of the previous embodiments, the first cosmetic protein comprises a sequence with 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 with an amino acid sequence selected from SEQ ID NOS: 15-21 and 53-64.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, or a laminin protein (e.g., a human collagen protein, a human elastin protein, a human fibronectin protein, or a human laminin protein). In some embodiments, it can be combined with any of these. Petition 870260060403, dated 06 / 19 / 2026, page 19 / 300 / 237 previous modalities, the first collagen protein is a human collagen protein. In some embodiments that can be combined with any of the preceding embodiments, the first collagen protein is selected from an alpha-1(I) collagen polypeptide (COL1-1), an alpha-2(I) collagen polypeptide (COL1-2), an alpha-1(II) collagen polypeptide (COL2), an alpha-1(III) collagen polypeptide (COL3), an alpha-1(IV) collagen polypeptide (COL41), an alpha-2(IV) collagen polypeptide (COL4-2), an alpha-3(IV) collagen polypeptide (COL4-3), an alpha-4(IV) collagen polypeptide (COL4-4), an alpha-5(IV) collagen polypeptide (COL4-5), an alpha-6(IV) collagen polypeptide (COL4-6), an alpha-1(V) collagen polypeptide (COL5-1), or an alpha-2(V) collagen polypeptide. (COL5-2),a collagen alpha-3(V) chain polypeptide (COL5-3), a collagen alpha-1(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-1(XI) chain polypeptide (COL11-1), an alpha-2(XI) chain polypeptide of collagen (COL11-2), an alpha-1(XII) chain polypeptide of collagen (COL12), an alpha-1(XIII) chain polypeptide of collagen (COL13),an alpha-1(XIV) chain polypeptide of collagen (COL14), an alpha-1(XV) chain polypeptide of collagen (COL15), an alpha-1(XVI) chain polypeptide of collagen (COL16), an alpha-1(XVII) chain polypeptide of collagen (COL17), a Petition 870260060403, dated 06 / 19 / 2026, page. 20 / 300 / 237 collagen alpha-1(XVIII) chain polypeptide (COL18), collagen alpha-1(XIX) chain polypeptide (COL19), collagen alpha-1(XX) chain polypeptide (COL20), collagen alpha-1(XXI) chain polypeptide (COL21), collagen alpha-1(XXII) chain polypeptide (COL22), collagen alpha-1(XXIII) chain polypeptide (COL23), collagen alpha-1(XXIV) chain polypeptide (COL24), collagen alpha-1(XXV) chain polypeptide (COL25), collagen alpha-1(XXVI) chain polypeptide (COL26), collagen alpha-1(XXVII) chain polypeptide (COL27) and collagen alpha-1(XXVIII) chain polypeptide (COL28). In some modalities that can be combined with any of the previous modalities, the first collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1, and COL17.In some embodiments that can be combined with any of the previous embodiments, the first collagen protein comprises a sequence with 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 with an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments that can be combined with any of the previous embodiments, the first collagen protein is human COL3.In some embodiments that can be combined with any of the previous embodiments, the first collagen protein comprises a sequence with 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 with the amino acid sequence of SEQ ID NO: 17. In some embodiments that can be... Petition 870260060403, dated 19 / 06 / 2026, page 21 / 300 / 237 combined with any of the previous embodiments, the first cosmetic protein is not an alpha-1 (VII) chain polypeptide of collagen (COL7).

[0012] 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) another cosmetic protein; and (c) a linker polypeptide that links (a) to (b). In some embodiments, the other 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, and a fibrillin protein.In some embodiments, the other 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 other cosmetic protein is a collagen protein, an elastin protein, a fibronectin protein, or a laminin protein (e.g., a human collagen protein, a human elastin protein, a human fibronectin protein, or a human laminin protein).In some embodiments, the other collagen protein (e.g., another human collagen protein) is selected from COL1-1, COL1-2, COL2, COL3, COL4-1, COL4-2, COL4-3, COL4-4, COL4-5, COL46, 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 other collagen protein (e.g., another human collagen protein) is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1, COL7, and COL17. In some... Petition 870260060403, dated 06 / 19 / 2026, page 22 / 300 / 237 embodiments, the first cosmetic protein and the other cosmetic protein are different. In some embodiments, the first cosmetic protein is COL1-1 (e.g., human COL1-1) and the other cosmetic protein is COL1-2 (e.g., human COL1-2). In some embodiments, the binding polypeptide is a cleavable binding polypeptide. In some embodiments, the linker polypeptide comprises a sequence with 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 with a selected amino acid sequence SEQ ID NOS: 28-31.

[0013] In some embodiments that can be combined with any of the previous embodiments, the first polynucleotide encodes a polycistronic mRNA comprising: (a) an open first 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, and a fibrillin 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, or a laminin protein (e.g., a human collagen protein, a human elastin protein, a human fibronectin protein, or a human laminin protein). In some embodiments, the additional collagen protein (e.g., a protein of... Petition 870260060403, dated 06 / 19 / 2026, page. 23 / 300 / 237 additional human collagen) 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 collagen protein (e.g., an additional human collagen protein) is selected from COL1-1, COL1-2, COL3, COL41, 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 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 with a nucleic acid sequence selected from SEQ ID NO: 22 or SEQ ID NO: 23.

[0014] In some embodiments that can be combined with any of the previous 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, and a fibrillin 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 Petition 870260060403, dated 06 / 19 / 2026, page 24 / 300 / 237 fibrillin protein, etc.). In some embodiments, the second cosmetic protein is a collagen protein, an elastin protein, a fibronectin protein, or a laminin protein (for example, a human collagen protein, a human elastin protein, a human fibronectin protein, or a human laminin 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, 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 collagen protein (e.g., a second 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 and second cosmetic proteins are different. In some embodiments, the first cosmetic protein is COL1-1 (e.g., human COL1-1) and the second additional 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).

[0015] In some embodiments that can be combined with any of the previous embodiments, the recombinant herpesvirus genome has reduced cytotoxicity when introduced into a target cell, compared to a corresponding wild-type herpesvirus genome. In some embodiments, the target cell is an epidermal and / or dermal cell. In some embodiments, the target cell is a human cell. In some embodiments, the target cell is a fibroblast.

[0016] Other aspects of this disclosure relate to a virus. Petition 870260060403, dated 06 / 19 / 2026, page 25 / 300 / 237 herpes comprising any of the recombinant herpesvirus genomes described herein. In some aspects, the herpesvirus is a replication-competent virus. In some embodiments, the herpesvirus is defective in replication. In some embodiments, the herpesvirus is attenuated. In some embodiments that can be combined with any of the foregoing embodiments, the herpesvirus has reduced cytotoxicity compared to a corresponding wild-type herpesvirus. In some embodiments that can be combined with any of the foregoing embodiments, the herpesvirus 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 forms that can be combined with any of the previous forms, the herpes virus is a herpes simplex virus.In some forms, the herpes simplex virus is a type 1 herpes simplex virus (HSV-1), a type 2 herpes simplex virus (HSV-2), or any derivative thereof. In some forms, the herpes simplex virus is a type 1 herpes simplex virus (HSV-1).

[0017] Other aspects of the present disclosure relate to a composition comprising: (a) any of the recombinant herpesvirus genomes described herein and / or any of the herpesviruses described herein; and (b) an excipient. In some embodiments, the composition is sterile. In some embodiments that may be combined with any of the above embodiments, the composition is suitable for topical, transdermal, subcutaneous, intradermal, oral, intranasal, intratracheal, sublingual, buccal, rectal, vaginal, inhalation, intravenous, intra-arterial, intramuscular, intracardiac, intraosseous, intraperitoneal, transmucosal, intravitreal, subretinal, intra-articular, periarticular, local or epicutaneous administration. In some embodiments that may be combined with any of the above embodiments, the composition is suitable for administration Petition 870260060403, dated 06 / 19 / 2026, p. 26 / 300 / 237 intradermal. In some embodiments that can be combined with any of the above embodiments, the composition is suitable for superficial injection. In some embodiments that can be combined with any of the above embodiments, the composition is a cosmetic composition. In some embodiments that can be combined with any of the above embodiments, the composition is a skin care product.

[0018] Other aspects of this 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 medicine (e.g., for an aesthetic indication).

[0019] Other aspects of this 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).

[0020] Other aspects of this 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 the treatment of one or more signs or symptoms of dermatological aging.

[0021] Other aspects of the present disclosure relate to a method for intensifying, increasing, amplifying 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.

[0022] Other aspects of the present disclosure relate to a method for intensifying, increasing, amplifying and / or supplementing the levels of one or more collagen proteins in a subject, the method comprising Petition 870260060403, dated 06 / 19 / 2026, p. 27 / 300 / 237 administer to the subject an effective quantity of any of the herpes viruses described herein and / or any of the compositions described herein. In some embodiments, one or more collagen proteins are collagen 3. In some embodiments, endogenous collagen 3 levels are reduced as a result of chronological aging or photoaging.

[0023] Other aspects of the present disclosure relate to a method for intensifying, increasing, enlarging 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 subject's soft tissue.

[0024] Other aspects of the present disclosure relate to a method for improving the condition, quality and / or appearance of the skin 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 exposure to ultraviolet rays, rough texture, sagging skin, wrinkles or any combination thereof.

[0025] Other aspects of the present disclosure relate to a method for 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, one or more superficial depressions in the skin are selected from the group consisting of nasolabial folds, crow's feet, expression lines, worry lines, scars, glabellar lines, brow ptosis, lacrimal cavities, nasojugal lines, bunny lines, cheek / mid-face ptosis, marionette lines, poppy ripples, smile lines, lines of Petition 870260060403, dated 06 / 19 / 2026, p. 28 / 300 / 237 laughter, chin creases, neck lines, platysma bands and any combinations thereof.

[0026] Other aspects of the present disclosure relate to a method for increasing and / or improving at least one aspect of the texture, smoothness, elasticity 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.

[0027] In some modalities that can be combined with any of the above modalities, the subject's skin is aging. In some modalities that can be combined with any of the above modalities, the subject's skin has been damaged due to exposure to ultraviolet light. In some modalities that can be combined with any of the above modalities, the subject's skin is wrinkled.

[0028] Other aspects of the present disclosure relate to a method for reducing 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 modalities, the reduction of one or more dermatological signs of aging is indicated by: (a) treatment, reduction and / or prevention of fine lines and / or wrinkles; (b) reduction of skin pore size; (c) improvement in skin thickness, smoothness and / or firmness; (d) improvement in skin smoothness, elasticity and / or suppleness; (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 the appearance of skin contours; (i) restoration of skin radiance and / or clarity; (j) improvement in the appearance of skin reduced by aging and / or menopause; (k) improvement in skin hydration; (l) increase in skin elasticity and / or resilience; (m) treatment. Petition 870260060403, dated 06 / 19 / 2026, page 29 / 300 / 237 reduction and / or prevention of skin sagging; (n) improvement of skin firmness; (o) reduction of pigment spots, skin blemishes and / or scars (such as acne scars); (p) improvement of the optical properties of the skin by light diffraction or reflection; or (q) any combination thereof.

[0029] In some embodiments that can be combined with any of the above embodiments, the subject is a human. In some embodiments that can be combined with any of the above embodiments, the herpes virus or composition is administered topically, transdermally, subcutaneously, epicutaneously, intradermally, orally, sublingually, buccally, rectally, vaginally, intravenously, intra-arterially, intramuscularly, intraosseously, intracardially, intraperitoneally, transmucosally, intravitreally, subretinally, intra-articularly, periarticularly, locally, or via inhalation to the subject. In some embodiments that can be combined with any of the above embodiments, the herpes virus or composition is administered intradermally to the subject.In some embodiments that can be combined with any of the above embodiments, the herpes virus or composition is administered by superficial injection.

[0030] 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 can be combined with any of the above embodiments, the HSV is replication-defective. In some embodiments that can be combined with any of the above embodiments, the HSV is replication-competent. In some embodiments that can be. Petition 870260060403, dated 06 / 19 / 2026, p. 30 / 300 / 237 combined with any of the above modalities, HSV is a herpes simplex virus type 1, a herpes simplex virus type 2, or any derivative thereof.

[0031] 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 HSV / EBV hybrid amplicon, an HSV / EBV / RV hybrid amplicon, or an HSV / Sleeping Beauty hybrid amplicon.

[0032] 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 can be combined with any of the foregoing 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), Single Long Region (UL) 41, and UL55. In some embodiments that can be combined with any of the foregoing embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in one or both copies of the ICP4 gene.In some embodiments that can be combined with any of the previous embodiments, the genome of the recombinant herpes simplex virus comprises an inactivation mutation in the ICP22 gene. In some embodiments that can be combined with any of the previous embodiments, the genome of the recombinant herpes simplex virus comprises an inactivation mutation in the UL41 gene. In some embodiments that can be combined with any of the previous embodiments, the genome of the virus... Petition 870260060403, dated 06 / 19 / 2026, p. 31 / 300 / 237 recombinant herpes simplex comprises an inactivation mutation in the ICP0 gene. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP27 gene. In some embodiments that can be combined with any of the above embodiments, the inactivation mutation is a deletion of the coding sequence of the gene(s).

[0033] In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within a viral gene locus. In some embodiments that can be combined with any of the previous 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 can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within the ICP22 viral gene locus. In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within the UL41 viral gene locus.In some modalities that can be combined with any of the previous modalities, HSV has reduced cytotoxicity compared to a wild-type herpes simplex virus.

[0034] In some embodiments that can be combined with any of the previous embodiments, the first human collagen protein is selected from an alpha-1 chain polypeptide (I) of collagen (COL11), an alpha-2 chain polypeptide (I) of collagen (COL1-2), an alpha-1 chain polypeptide (II) of collagen (COL2), an alpha-1 chain polypeptide (III) of collagen (COL3), an alpha-1 chain polypeptide (IV) of collagen (COL41), an alpha-2 chain polypeptide (IV) of collagen (COL4-2), a Petition 870260060403, dated 06 / 19 / 2026, page. 32 / 300 / 237 collagen alpha-3(IV) chain polypeptide (COL4-3), collagen alpha-4(IV) chain polypeptide (COL4-4), collagen alpha-5(IV) chain polypeptide (COL4-5), collagen alpha-6(IV) chain polypeptide (COL4-6), collagen alpha-1(V) chain polypeptide (COL5-1), collagen alpha-2(V) chain polypeptide (COL5-2), collagen alpha-3(V) chain polypeptide (COL5-3), collagen alpha-1(VI) chain polypeptide (COL6-1), collagen alpha-2(VI) chain polypeptide (COL6-2), collagen alpha-3(VI) chain polypeptide (COL6-3), collagen alpha-4(VI) chain polypeptide (COL6-4), collagen alpha-5(VI) chain polypeptide (COL6-5), collagen chain polypeptide alpha-6(VI) collagen (COL6-6), an alpha-1(VII) collagen chain polypeptide (COL7), an alpha-1(VIII) collagen chain polypeptide (COL8), an alpha-1(IX) collagen chain polypeptide (COL9-1),an alpha-2 chain polypeptide (IX) of collagen (COL9-2), an alpha-3 chain polypeptide (IX) of collagen (COL9-3), an alpha-1 chain polypeptide (X) of collagen (COL10), an alpha-1 chain polypeptide (XI) of collagen (COL11-1), an alpha-2 chain polypeptide (XI) of collagen (COL11-2), an alpha-1 chain polypeptide (XII) of collagen (COL12), an alpha-1 chain polypeptide (XIII) of collagen (COL13), an alpha-1 chain polypeptide (XIV) of collagen (COL14), an alpha-1 chain polypeptide (XV) of collagen (COL15), an alpha-1 chain polypeptide (XVI) of collagen (COL16), an alpha-1 chain polypeptide (XVII) of collagen (COL17), an alpha-1 chain polypeptide (XVIII) of collagen (COL18), an alpha-1 chain polypeptide (XIX) of collagen (COL19), an alpha-1(XX) chain polypeptide of collagen (COL20), an alpha-1(XXI) chain polypeptide of collagen (COL21), an alpha-1(XXII) chain polypeptide of collagen (COL22),an alpha-1(XXIII) chain polypeptide of collagen (COL23), an alpha-1(XXIV) chain polypeptide of collagen (COL24), an alpha-1(XXV) chain polypeptide of collagen (COL25), an alpha-1(XXVI) chain polypeptide of, Petition 870260060403, dated 06 / 19 / 2026, p. 33 / 300 / 237 collagen (COL26), an alpha-1 chain polypeptide (XXVII) of collagen (COL27) and an alpha-1 chain polypeptide (XXVIII) of collagen (COL28). In some embodiments that can be combined with any of the previous 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 can be combined with any of the previous 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 with a selected nucleic acid sequence from SEQ ID NOS: 1-14.In some embodiments that can be combined with any of the foregoing embodiments, the first human collagen protein comprises a sequence with 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 with an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments that can be combined with any of the foregoing embodiments, the first human collagen protein is not COL7.

[0035] In some embodiments that can be combined with any of the foregoing embodiments, the first polypeptide comprises: (a) the first human collagen protein; (b) another human collagen protein; and (c) a linker polypeptide that links (a) to (b). In some embodiments, the linker polypeptide is a cleavable linker polypeptide.In some embodiments, the linker polypeptide comprises a sequence with 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... Petition 870260060403, dated 06 / 19 / 2026, page 34 / 300 / 237 100% sequence identity with a selected amino acid sequence from SEQ ID NOS: 28-31. In some embodiments, the other human collagen protein is selected from COL1-1, COL1-2, COL2, COL3, COL41, 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, COL91, 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 other 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 other 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 with a selected nucleic acid sequence from SEQ ID NOS: 1-14. In some embodiments, the other human collagen protein comprises a sequence with 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 with a selected amino acid sequence from SEQ ID NOS: 15-21. In some embodiments, the first human collagen protein and the additional human collagen protein are different.

[0036] In some embodiments that can be combined with any of the preceding embodiments, the first polynucleotide encodes a polycistronic mRNA comprising: (a) an open first 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 Petition 870260060403, dated 06 / 19 / 2026, page. The 35 / 300 / 237 nucleic acid sequence encoding 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 with 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, COL93, 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, additional human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL61, 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 with a selected nucleic acid sequence from SEQ ID NOS: 1-14. In some embodiments, the additional human collagen protein comprises a sequence with 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 with 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.

[0037] In some embodiments that can be combined with any of the above embodiments, recombinant nucleic acid Petition 870260060403, dated 06 / 19 / 2026, page 36 / 300 / 237, also includes a second polynucleotide that codes for 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, COL93, 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, COL61, 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 with a selected nucleic acid sequence from SEQ ID NOS: 1-14. In some embodiments, the second human collagen protein comprises a sequence with 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 with a selected amino acid sequence from SEQ ID NOS: 15-21. In some embodiments, the first and second human collagen proteins are different.

[0038] In some embodiments that can be combined with any of the previous embodiments, the recombinant nucleic acid is a recombinant herpes simplex virus genome, and in that the recombinant herpes simplex virus genome comprises the second polynucleotide within a viral gene locus. In some embodiments, the herpes simplex virus genome Petition 870260060403, dated 06 / 19 / 2026, page 37 / 300 / 237 recombinant simplex comprises the second polynucleotide in one or both copies of the viral gene loci ICP4. In some embodiments, the recombinant herpes simplex virus genome comprises the second polynucleotide within the viral gene locus ICP22. In some embodiments, the recombinant herpes simplex virus genome comprises the second polynucleotide within the viral gene locus UL41. In some embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within one or both copies of the viral gene loci ICP4 and the second polynucleotide within the viral gene locus ICP22. 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.

[0039] In some embodiments that can be combined with any of the previous embodiments, the excipient is adapted for cutaneous (systemic or topical), transdermal, subcutaneous and / or intradermal administration. In some embodiments that can be combined with any of the previous embodiments, the excipient comprises a hydroxypropyl methylcellulose gel. In some embodiments that can be combined with any of the previous embodiments, the excipient is adapted for intradermal administration. In some embodiments that can be combined with any of the previous embodiments, the excipient comprises a phosphate buffer. In some embodiments that can be combined with any of the previous embodiments, the excipient comprises glycerol. In some embodiments that can be combined with any of the previous embodiments, the excipient comprises a lipid carrier.In some embodiments that can be combined with any of the above embodiments, the excipient comprises a nanoparticle carrier.

[0040] In some modalities that can be combined with Petition 870260060403, dated 06 / 19 / 2026, p. 38 / 300 / 237 In any of the above modalities, the composition is a cosmetic composition. In some modalities, the cosmetic composition is a skin care product.

[0041] Other aspects of this disclosure relate to a kit comprising any of the compositions described herein and instructions for administering the composition.

[0042] Other aspects of the present disclosure relate to a method for intensifying, increasing, amplifying and / or supplementing the levels of one or more human collagen proteins in a subject, the method comprising administering to the subject an effective amount of any of the compositions described herein.

[0043] Other aspects of the present disclosure relate to a method for enhancing, increasing, enlarging and / or supplementing the 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 the subject's soft tissue.

[0044] Other aspects of the present disclosure relate to a method for improving the quality, condition, and / or appearance of the skin 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, sagging skin, wrinkles, and any combination thereof.

[0045] Other aspects of the present disclosure relate to a method for 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 one or more superficial depressions in the subject's skin by Petition 870260060403, dated 06 / 19 / 2026, page 39 / 300 / 237 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 one or more superficial depressions on the subject's skin is reduced after administration of the composition, compared to the appearance of one or more superficial depressions on the subject's skin before administration of the composition.

[0046] Other aspects of the present disclosure relate to a method for increasing and / or improving at least one of the texture, smoothness, elasticity, 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 compositions described herein. In some embodiments, the subject's skin maintains at least one of the increased and / or improved texture, smoothness, elasticity, 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 the subject's skin texture, smoothness, elasticity, or tension is increased and / or improved after administration of the composition, compared with the subject's skin texture, smoothness, elasticity, or tension before administration of the composition.

[0047] In some modalities that can be combined with any of the above modalities, the subject's skin is aging. In some modalities that can be combined with any of the above modalities, the subject's skin has been damaged due to exposure to ultraviolet light. In some modalities that can be combined with any of the above modalities, the subject's skin is wrinkled.

[0048] Other aspects of the present disclosure relate to a method for reducing 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. Petition 870260060403, dated 06 / 19 / 2026, p. 40 / 300 / 237 In some modalities, the reduction 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, smoothness and / or firmness; (d) improvement in skin smoothness, elasticity and / or suppleness; (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 the appearance of skin contours; (i) restoration of skin radiance and / or clarity; (j) improvement in the appearance of skin reduced by aging and / or menopause; (k) improvement in skin hydration; (l) increase in skin elasticity and / or resilience; (m) treatment, reduction and / or prevention of skin sagging; (n) improvement in skin firmness; (o) reduction of pigment spots, skin blemishes and / or acne scars);(p) improvement of the optical properties of the skin by light diffraction or reflection; and (q) any combination thereof. In some embodiments, one or more dermatological signs of aging in the subject are reduced after administration of the composition, compared to one or more dermatological signs of aging in the subject before administration of the composition.

[0049] In some embodiments that can be combined with any of the above embodiments, the subject is a human. In some embodiments that can be combined with any of the above embodiments, the composition is administered cutaneously (systemically or topically), transdermally, subcutaneously, or intradermally to the subject. In some embodiments, the compositions are administered by intravenous injection. In some embodiments, a subject antibody composition is administered intracranially. In some embodiments, a subject antibody composition is administered orally. In some embodiments, the composition is administered at least twice to the subject. In some embodiments, at least about 15, at least about 30, Petition 870260060403, dated 06 / 19 / 2026, p. 41 / 300 / 237 at least approximately 60, at least approximately 90, or at least approximately 120 days pass between administrations. In some modalities that can be combined with any of the above modalities, the composition is administered to one or more affected and / or unaffected areas of the subject. In some modalities that can be combined with any of the previous modalities, the skin is shaved before administration.

[0050] 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.

[0051] In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises an inactivation 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), Single Long Region (UL) 41, and UL55. In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in one or both copies of the ICP4 gene. In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP22 gene. In some embodiments that can be combined with any of the previous embodiments, the genome of the recombinant herpes simplex virus comprises a Petition 870260060403, dated 06 / 19 / 2026, p. 42 / 300 / 237 inactivation mutation in the UL41 gene. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP0 gene. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP27 gene. In some embodiments that can be combined with any of the above embodiments, the inactivation mutation is a deletion of the coding sequence of the gene(s).

[0052] In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within a viral gene locus. In some embodiments that can be combined with any of the previous 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 can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within the ICP22 viral gene locus. In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within the UL41 viral gene locus.In some modalities that can be combined with any of the previous modalities, HSV has reduced cytotoxicity compared to a wild-type herpes simplex virus.

[0053] In some embodiments that can be combined with any of the previous 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 Petition 870260060403, dated 06 / 19 / 2026, page 43 / 300 / 237 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 can 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 can be combined with any of the previous 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 with a selected nucleic acid sequence from SEQ ID NOS: 1-14.In some embodiments that can be combined with any of the previous embodiments, the first human collagen protein comprises a sequence with 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 with an amino acid sequence selected from SEQ ID NOS: 15-21. In some embodiments that can be combined with any of the previous embodiments, the first human collagen protein is not COL7.

[0054] In some embodiments that can be combined with any of the preceding embodiments, the first polypeptide comprises: (a) the first human collagen protein; (b) another human collagen protein; and (c) a linker polypeptide that links (a) to (b). In some embodiments, the linker polypeptide is a cleavable linker polypeptide. In some embodiments, the linker polypeptide comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least Petition 870260060403, dated 06 / 19 / 2026, page 44 / 300 / 237 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with a selected amino acid sequence from SEQ ID NOS: 28-31. In some embodiments, the other human collagen protein is selected from COL1-1, COL1-2, COL2, COL3, COL41, 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, COL91, 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 other 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 other 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 with a selected nucleic acid sequence from SEQ ID NOS: 1-14. In some embodiments, the other human collagen protein comprises a sequence with 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 with a selected amino acid sequence from SEQ ID NOS: 15-21. In some embodiments, the first human collagen protein and the additional human collagen protein are different.

[0055] In some embodiments that can be combined with any of the preceding embodiments, the first polynucleotide encodes a polycistronic mRNA comprising: (a) an open first reading frame (ORF) encoding the first polypeptide; (b) a second ORF encoding an additional human collagen protein; and (c) an entry site. Petition 870260060403, dated 06 / 19 / 2026, page 45 / 300 / 237 internal ribosomal (IRES) separating (a) and (b). In some embodiments, the nucleic acid sequence encoding 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 with 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, COL93, 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, COL61, 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 with a nucleic acid sequence selected from SEQ ID NOS: 1-14. In some embodiments, the additional human collagen protein comprises a sequence with 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 with an amino acid sequence selected from SEQ ID NOS: 15-21.In some forms, the primary human collagen protein and the additional human collagen protein are different.

[0056] In some modalities that can be combined with Petition 870260060403, dated 06 / 19 / 2026, page 46 / 300 / 237 In any of the previous embodiments, the recombinant nucleic acid further comprises a second polynucleotide that encodes 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, COL93, 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, COL61, 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 with a selected nucleic acid sequence from SEQ ID NOS: 1-14. In some embodiments, the second human collagen protein comprises a sequence with 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 with a selected amino acid sequence from SEQ ID NOS: 15-21. In some embodiments, the first and second human collagen proteins are different.

[0057] In some embodiments that can be combined with any of the previous embodiments, the recombinant herpes simplex virus genome comprises the second polynucleotide within a viral gene locus. In some embodiments, the herpes simplex virus genome Petition 870260060403, dated 06 / 19 / 2026, page 47 / 300 / 237 recombinant comprises the second polynucleotide in one or both copies of the viral gene loci ICP4. In some embodiments, the recombinant herpes simplex virus genome comprises the second polynucleotide within the viral gene locus ICP22. In some embodiments, the recombinant herpes simplex virus genome comprises the second polynucleotide within the viral gene locus UL41. In some embodiments, the recombinant herpes simplex virus genome comprises the first polynucleotide within one or both copies of the viral gene loci ICP4 and the second polynucleotide within the viral gene locus ICP22. 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.

[0058] 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 eukaryotic. In some embodiments, the cell is a mammalian cell. In some embodiments, the cell is a human cell. In some embodiments, the host cell is a Vero cell. In some embodiments, the host cell is a complementary host cell.

[0059] Other aspects of the present disclosure relate to a method of collecting a herpes simplex virus, the method comprising: (a) contacting a complementary host cell with any of the recombinant nucleic acids described herein; and (b) collecting the herpes simplex virus generated by the complementary host cell.

[0060] 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. Petition 870260060403, dated 06 / 19 / 2026, page 48 / 300 / 237 BRIEF DESCRIPTION OF THE DRAWINGS

[0061] The patent application or publication file contains at least one figure executed in color. Copies of such patent or patent application publication with color figures will be provided by the Office upon request and payment of the necessary fee.

[0062] FIGS. 1A-N show schematic genomes of wild-type and modified herpes simplex viruses.

[0063] FIG. 1A shows a wild-type herpes simplex virus genome.

[0064] FIG. 1B 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 polypeptide operationally linked to a heterologous promoter integrated into each of the ICP4 loci.

[0065] FIG. 1C shows a modified herpes simplex virus genome comprising deletions of the ICP4 coding sequence (both copies), with a polynucleotide containing the coding sequence of a first human collagen polypeptide operationally linked to a heterologous promoter integrated into each of the ICP4 loci.

[0066] FIG. 1D 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 polypeptide operationally linked to a first heterologous promoter, and 2) the coding sequence of a second human collagen polypeptide operationally linked to a second heterologous promoter, integrated into each of the ICP4 loci. Both the first and second polypeptides of Petition 870260060403, dated 06 / 19 / 2026, page 49 / 300 / 237: human collagen is encoded on the same DNA strand.

[0067] FIG. 1E shows a modified herpes simplex virus genome comprising deletions of the ICP4 coding sequence (both copies), with a polynucleotide containing 1) the coding sequence of a first human collagen polypeptide operationally linked to a first heterologous promoter, and 2) the coding sequence of a second human collagen polypeptide operationally linked to a second heterologous promoter, integrated into each of the ICP4 loci. Both the first and second human collagen polypeptides are encoded on the same DNA strand.

[0068] FIG. 1F 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 polypeptide operationally linked to a first heterologous promoter, and 2) the coding sequence of a second human collagen polypeptide operationally linked to a second heterologous promoter, integrated into each of the ICP4 loci. The first and second human collagen polypeptides are encoded on opposite strands of DNA.

[0069] FIG. 1G shows a modified herpes simplex virus genome comprising deletions of the ICP4 coding sequence (both copies), with a polynucleotide containing 1) the coding sequence of a first human collagen polypeptide operationally linked to a first heterologous promoter, and 2) the coding sequence of a second human collagen polypeptide operationally linked to a second heterologous promoter, integrated into each of the ICP4 loci. The first and second human collagen polypeptides are encoded on opposite strands of DNA.

[0070] FIG. 1H shows a herpes simplex virus genome. Petition 870260060403, dated 06 / 19 / 2026, page 50 / 300 / 237, modified, comprising deletions of the coding sequences of ICP4 (both copies) and ICP22, with a polynucleotide encoding a polycistronic mRNA operationally linked to a heterologous promoter integrated into each of the ICP4 loci. The polycistronic mRNA contains the coding sequence of a first human collagen polypeptide and a second human collagen polypeptide separated by an internal ribosomal entry site (IRES).

[0071] FIG. 1I shows a modified herpes simplex virus genome comprising deletions of the ICP4 coding sequence (both copies), with a polynucleotide encoding a polycistronic mRNA operationally linked to a heterologous promoter integrated into each of the ICP4 loci. The polycistronic mRNA contains the coding sequence of a first human collagen polypeptide and a second human collagen polypeptide separated by an internal ribosomal entry site (IRES).

[0072] FIG. 1J shows a modified herpes simplex virus genome comprising deletions of the ICP4 (both copies) and ICP22 coding sequences, with a polynucleotide containing the coding sequence of a chimeric polypeptide operationally linked to a heterologous promoter integrated into each of the ICP4 loci.The chimeric polypeptide comprises the amino acid sequence of a first human collagen polypeptide and a second human collagen polypeptide separated by a cleavable linker.

[0073] FIG. 1K shows a modified herpes simplex virus genome comprising deletions of the ICP4 coding sequence (both copies), with a polynucleotide containing the coding sequence of a chimeric polypeptide operationally linked to a heterologous promoter integrated into each of the ICP4 loci. The chimeric polypeptide comprises the amino acid sequence of a first human collagen polypeptide and a second collagen polypeptide. Petition 870260060403, dated 06 / 19 / 2026, page 51 / 300 / 237 human separated by a cleavable ligand.

[0074] FIG. 1L 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 polypeptide operationally linked to a heterologous promoter integrated into each of the ICP4 loci, and a second polynucleotide containing the coding sequence of a second human collagen polypeptide operationally linked to a heterologous promoter integrated into the ICP22 locus.

[0075] FIG. 1M 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 polypeptide operationally linked to a heterologous promoter integrated into each of the ICP4 loci and a second polynucleotide containing the coding sequence of a second human collagen polypeptide operationally linked to a heterologous promoter integrated into the UL41 locus.

[0076] FIG. 1N 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 polypeptide operationally linked to a heterologous promoter integrated into each of the ICP4 loci, and a second polynucleotide containing the coding sequence of a second human collagen polypeptide operationally linked to a heterologous promoter integrated into the UL41 locus.

[0077] FIGS. 2A-B show schematic diagrams of replication-defective herpes simplex virus type 1 carrying human collagen 7 (COL7) expression cassettes.

[0078] FIG. 2A shows a schematic of the “KCA211” virus. Petition 870260060403, dated 06 / 19 / 2026, page 52 / 300 / 237

[0079] FIG. 2B shows a diagram of the “SAR-COL7” virus.

[0080] FIGS. 3A-B show the expression of human COL7 in HaCaT cells infected with KCA211 or SAR-COL7 in the indicated MOIs.

[0081] FIG. 3A shows the expression of human COL7 in HaCaT cells infected with KCA211 or SAR-COL7 in the indicated MOIs, as assessed by qPCR. Data are presented as changes in times relative to SAR-COL7, after normalization for GAPDH.

[0082] FIG. 3B shows the expression of human COL7 in uninfected HaCaT cells or HaCaT cells infected with KCA211 or SARCOL7 in the indicated MOIs, as assessed by Western blot analysis.

[0083] FIGS. 4A-B show immunofluorescence images of human COL7 expression in sham-infected primary human cells isolated from a healthy patient (Normal) and SAR-COL7-infected or sham-infected primary human cells isolated from a patient suffering from recessive dystrophic epidermolysis bullosa (RDEB).

[0084] FIG. 4A shows the expression of human COL7 in sham-infected RDEB and wild-type primary human keratinocytes, or in SAR-COL7-infected RDEB primary human keratinocytes at the indicated multiplicity of infections (MOIs).

[0085] FIG. 4B shows the expression of human COL7 in primary human wild-type and RDEB fibroblasts with sham infection, or in primary human RDEB fibroblasts infected with SAR-COL7 in the indicated MOIs.

[0086] FIGS. 5A-B show quantitative PCR analysis of human COL7 expression in sham-infected primary human cells isolated from a healthy patient and sham-infected primary human cells or SAR-COL7 isolated from a patient suffering from recessive dystrophic epidermolysis bullosa (EB).

[0087] FIG. 5A shows the expression of human COL7 in Petition 870260060403, dated 06 / 19 / 2026, p. 53 / 300 / 237 primary human keratinocytes with sham wild-type (NHDK) and RDEB (EB-HDK) infection, or in primary human RDEB keratinocytes infected with SAR-COL7 in the indicated MOIs. COL7 expression is shown as the relative change from sham wild-type primary human keratinocytes.

[0088] FIG. 5B shows the expression of human COL7 in sham-infected primary human fibroblasts (N-HDF) and RDEB (EB-HDF), or in SAR-COL7-infected primary human RDEB fibroblasts at the indicated MOIs. COL7 expression is shown as the relative change from sham-infected wild-type primary human fibroblasts.

[0089] FIGS. 6A-B show cell adhesion of uninfected (control) or SARCOL7-infected primary human RDEB keratinocytes to untreated (plastic) or treated wells of a microwell plate.

[0090] FIG. 6A shows cell adhesion to untreated (plastic) wells, or wells treated with increasing concentrations of rat tail Collagen 1.

[0091] FIG. 6B shows cell adhesion to untreated wells (plastic), or wells treated with increasing concentrations of human plasma fibronectin.

[0092] FIG. 7 shows immunofluorescence images representative of the expression and deposition of human COL7 in the basement membrane zone (BMZ) on day 5 in organotypic cultures constructed with primary human RDEB keratinocytes and fibroblasts infected with SAR-COL7. Both keratinocytes and fibroblasts were infected in situ at the indicated MOI after culture construction.

[0093] FIGS. 8A-D show transcript and genome levels of human COL7A1 observed in the skin of uninfected mice (control), or in mouse skin after topical or intradermal application of SAR-COL7, Petition 870260060403, dated 06 / 19 / 2026, page 54 / 300 / 237 as assessed by qPCR. Error bars represent SEM.

[0094] FIG. 8A shows the levels of human COL7A1 transcripts / 100 ng of total RNA in mouse skin on day 3 after infection.

[0095] FIG. 8B shows the number of copies of human COL7A1 DNA / total DNA of 100 ng in mouse skin on day 3 after infection.

[0096] FIG. 8C shows the levels of human COL7A1 transcripts / 100ng of total RNA in mouse skin on day 6 after infection.

[0097] FIG. 8D shows the number of copies of human COL7A1 DNA / total DNA of 100 ng in mouse skin on day 6 after infection.

[0098] FIGS. 9A-B show immunofluorescence images representative of human COL7 expression in mouse skin after SAR-COL7 delivery.

[0099] FIG. 9A shows a representative immunofluorescent image of human COL7 expression in mouse skin after intradermal delivery of SAR-COL7.

[00100] FIG. 9B shows a representative immunofluorescent image of human COL7 expression in mouse skin after topical application of SAR-COL7.

[00101] FIGS. 10A-B show human COL7A1 transcripts and genome levels observed in BALB / c mouse skin after intradermal delivery of vehicle, SAR-COL7, or KCA211, as assessed by qPCR.

[00102] FIG. 10A shows the levels of human COL7A1 transcripts / 100 ng of total RNA in BALB mouse skin / c.

[00103] FIG. 10B shows the number of copies of human COL7A1 DNA / 100 ng of total DNA in BALB mouse skin / c.

[00104] FIGS. 11A-B show the transcript and genome levels of human COL7A1 observed at each injection site in hypomorphic mouse skin after high-dose intradermal delivery of HSV-GFP (GFP ctrl) Petition 870260060403, dated 06 / 19 / 2026, page 55 / 300 / 237 or SAR-COL7, as assessed by qPCR. Each bar represents a single sample at the indicated time point.

[00105] FIG. 11A shows the levels of human COL7A1 transcripts / 100 ng of total RNA in hypomorphic mouse skin.

[00106] FIG. 11B shows the number of human COL7A1 DNA copies / 100 ng of total DNA in hypomorphic mouse skin.

[00107] FIGS. 12A-B show immunofluorescence images representative of human COL7 expression in hypomorphic mouse skin after intradermal delivery of a high dose of HSV-GFP (GFP Control) or SAR-COL7.

[00108] FIG. 12A shows immunofluorescence imaging of control (GFP) and SAR-COL7 from hypomorphic mouse 1 (collected on day 3) at 10x and 20x magnification.

[00109] FIG. 12B shows SARCOL7 immunofluorescence images from hypomorphic mouse 2 and hypomorphic mouse 3 (collected on day 7). The figure represents a side-by-side image of 16 fields acquired with a 10x lens, capturing the entire skin section.

[00110] FIG. 13 shows H&E-stained samples from hypomorphic mice 1, 2, and 3 (collected on days 3 and 3). Samples were taken from untreated hypomorphic mouse skin and hypomorphic mouse skin after intradermal distribution of HSV-GFP or SAR-COL7.

[00111] FIGS. 14A-B show representative electron micrograph images of human COL7 expression in hypomorphic mouse skin after intradermal distribution of SAR-COL7. The lamina densa is the dark band indicated in the middle of the images; the black dots are the stained NC domains of human COL7; the blue arrows indicate the formation of anchoring fibrils.

[00112] FIG. 14A shows electron micrograph images of skin from an infected hypomorphic mouse, stained with a specific antibody for the Petition 870260060403, dated 06 / 19 / 2026, page 56 / 300 / 237 NC2 domain of human COL7 (LH24).

[00113] FIG. 14B shows electron micrograph images of infected hypomorphic mouse skin stained with an antibody specific for the NC1 domain of human COL7 (NP185).

[00114] FIGS. 15A-B show the levels of human COL7A1 transcript and genome observed at each injection site in hypomorphic mouse skin after low-dose intradermal delivery of SAR-COL7, as assessed by qPCR. Each bar represents a single sample at the indicated time point.

[00115] FIG. 15A shows the levels of human COL7A1 transcripts / 100 ng of total RNA in hypomorphic mouse skin.

[00116] FIG. 15B shows the number of human COL7A1 DNA copies / 100 ng of total DNA in hypomorphic mouse skin.

[00117] FIG. 16 shows immunofluorescence images representative of human COL7 expression in hypomorphic mouse skin (from mouse 1) after low-dose intradermal delivery of SAR-COL7.

[00118] FIGS. 17A-C show analyses of human COL1A1 and COL1A2 nucleic acids and proteins in Vero cells infected with the indicated HSV clones encoding COL1A1 alone (inserted into ICP4 loci) or COL1A1 and COL1A2 (inserted into ICP4 and ICP2 loci, respectively).

[00119] FIG. 17A 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 are shown for two replicates ± SEM.

[00120] FIG. 17B 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 are shown for two replicates ± SEM.

[00121] FIG. 17C shows the Western blot analysis of the expression of Petition 870260060403, dated 06 / 19 / 2026, page 57 / 300 / 237 human COL1A1 and COL1A2 protein in Vero cells 5 days after infection with the indicated COL1A1 / COL1A2 positive clones, as determined by qRT-PCR. Uninfected (sham) Vero cells were used as a negative control; GAPDH was used as a loading control.

[00122] FIG. 18 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-IRESCOL1A2 sequence (IRES-Isolate 6) inserted into ICP4 loci. Infection with an isolate lacking the IRES construct (no insertion) was used as a negative control; GAPDH was used as a loading control.

[00123] FIGS. 19A-B show analyses of human COL3 protein and nucleic acid in immortalized human keratinocytes (HaCaTs) infected with C3vec01.

[00124] FIG. 19A shows the levels of human COL3A1 transcripts present in immortalized human keratinocytes (HKs) after infection with C3vec01 in the indicated MOIs. Uninfected (sham) and HSV-mCherry (mCherry) infected cells were used as negative controls. Data are presented for two replicates ± SEM.

[00125] FIG. 19B shows immunofluorescence images representative of human COL3 protein expression in human keratinocytes immortalized 48 hours after infection with C3vec01 in the indicated MOIs. Uninfected (sham) cells were used as negative controls.

[00126] FIGS. 20A-B show analyses of human COL3 protein and nucleic acid in immortalized human dermal fibroblasts (HDFs) infected with C3vec01.

[00127] FIG. 20A shows the levels of human COL3A1 transcripts present in immortalized human dermal fibroblasts (HDFs) after infection with C3vec01 in the indicated MOIs. Uninfected (simulated) cells Petition 870260060403, dated 06 / 19 / 2026, page 58 / 300 / 237 and infected with HSV-mCherry (mCherry) were used as negative controls. Data are presented for two replicates ± SEM.

[00128] FIG. 20B shows immunofluorescence images representative of human COL3 protein expression in human dermal fibroblasts immortalized 48 hours after infection with C3vec01 in the indicated MOIs. Uninfected (sham) cells were used as negative controls.

[00129] FIGS. 21A-D show nucleic acid and human COL3 protein analyses in aged primary human fibroblasts (HDFs) from two different suppliers infected with C3vec01 at the indicated MOIs.

[00130] FIG. 21A shows the levels of human COL3A1 transcripts present in primary HDFs harvested from a 65-year-old female patient or a 73-year-old male patient (provider 1) after infection with C3vec01 in the indicated MOIs. Untransfected (sham) cells were used as a negative control. Data are presented for two replicates ± SEM.

[00131] FIG. 21B shows Western blot analysis of human COL3A1 protein expression in primary HDFs harvested from a 73-year-old male patient (provider 1) after infection with C3vec01 in the indicated MOIs. Uninfected (sham) cells were used as a negative control; recombinant human COL3A1 (rCOL3A1) was used as a positive control; GAPDH was used as a loading control.

[00132] FIG. 21C shows the levels of human COL3A1 transcripts present in primary HDFs harvested from a 75-year-old female patient or a 73-year-old male patient (provider 2) after infection with C3vec01 in the indicated MOIs. Untransfected (sham) CHO cells were used as a negative control. Data are presented for two replicates ± SEM. Petition 870260060403, dated 06 / 19 / 2026, page 59 / 300 / 237

[00133] FIG. 21D shows Western blot analysis of human COL3A1 protein expression in primary HDFs harvested from a 75-year-old female patient (provider 2) after infection with C3vec01 in the indicated MOIs. Uninfected (sham) cells were used as a negative control; recombinant human COL3A1 (rCOL3A1) was used as a positive control; GAPDH was used as a loading control.

[00134] FIGS. 22A-B show analyses of human COL3 protein and nucleic acid in immortalized human dermal fibroblasts (HDFs) after UV exposure.

[00135] FIG. 22A shows the concentration of COL3 secreted in the supernatant of cultured HDFs 24 hours after exposure to various dosages and times of UV light, as assessed by ELISA. The supernatant collected from non-UV exposed HDFs (-UV) cultured in parallel was used as a control.

[00136] FIG. 22B shows the levels of human COL3A1 transcripts present in immortalized human dermal fibroblasts (HDFs) exposed to UV after infection with C3vec01 in the indicated MOIs. Uninfected (sham) and HSV-mCherry (mCherry) infected cells were used as negative controls. Data are presented for two replicates ± SEM.

[00137] FIGS. 23A-C show nucleic acid and COL3 protein analyses of skin biopsies taken from young (6-8 weeks old) and old (~13 months old) C57BL / 6 mice treated with control or C3vec01 48 hours after intradermal application.

[00138] FIG. 23A shows the levels of human COL3A1 DNA present in skin biopsies taken from young and old mice 48 hours after intradermal administration of C3vec01 or vehicle control, as assessed by qPCR analysis.

[00139] FIG. 23B shows the levels of human COL3A1 transcripts present in skin biopsies taken from young and old mice 48 Petition 870260060403, dated 06 / 19 / 2026, page 60 / 300 / 237 hours after intradermal administration of C3vec01 or vehicle control, as assessed by qRT-PCR analysis. For each condition in the qPCR and qRT-PCR analysis, data are presented as the average of four tissue samples (two replicates / tissue sample) ± SEM.

[00140] FIG. 23C shows representative immunofluorescence images of human COL3 expression in skin biopsies taken from young and old mice 48 hours after intradermal administration of C3vec01. A young mouse administered intradermally alone was used as a negative control. DAPI staining was used to visualize the nuclei.

[00141] FIGS. 24A-B show the expression of wild-type (WT) human LamB3 in Vero cells infected with the indicated viral isolates.

[00142] FIG. 24A shows the expression of wild-type human LAMB3 in infected Vero cells, as assessed by qPCR analysis.

[00143] FIG. 24B shows the expression of wild-type human LamB3 protein in infected Vero cells, as assessed by Western blot.

[00144] FIG. 25 shows the expression of wild-type (WT) or codon-optimized (CO) human LamB3 protein in Vero cells infected with the indicated viral isolates, as assessed by western blot. Untransfected Vero CHO cells were used as a negative control.

[00145] FIG. 26 shows the expression of wild-type (WT) or codon-optimized (CO) human LamB3 protein in primary human keratinocytes infected with the indicated viral isolates, as assessed by western blot. Uninfected primary keratinocytes were used as a negative control.

[00146] FIGS. 27A-C show expression of wild-type (WT) and codon-optimized (CO) human LamC2 in Vero cells infected with the indicated viral isolates.

[00147] FIG. 27A shows the expression of human LAMC2 type Petition 870260060403, dated 06 / 19 / 2026, page 61 / 300 / 237 wild type in infected Vero cells, as assessed by qPCR analysis.

[00148] FIG. 27B shows codon-optimized human LAMC2 expression in infected Vero cells, as assessed by qPCR analysis.

[00149] FIG. 27C shows the expression of wild-type and codon-optimized human LamC2 protein in infected Vero cells, as assessed by western blot. The LGA boxed viral isolate expressing codon-optimized LamC2 was selected for further experimentation.

[00150] FIGS. 28A-C show human LAMC2 expressed from LGA viral isolate in infected immortalized primary human keratinocytes at the indicated multiplicities of infection (MOIs).

[00151] FIG. 28A shows the number of copies of the viral genome in primary immortalized human keratinocytes after infection with the LGA viral isolate in the indicated MOIs.

[00152] FIG. 28B shows the codon-optimized LAMC2 transcript level expressed in primary immortalized human keratinocytes after infection with LGA viral isolate in the indicated MOIs.

[00153] FIG. 28C shows the expression of human LamC2 protein in immortalized primary human keratinocytes after infection with LGA viral isolate in the indicated MOIs, as assessed by western blot.

[00154] FIGS. 29A-D show LAMC2 nucleic acid and protein analysis of skin biopsies taken from control (vehicle) - or mice treated with HSV-isolated LGA 72 hours after intradermal application.

[00155] FIG. 29A shows a diagram of the intradermal injection sites in the treated animals.

[00156] FIG. 29B shows the levels of human LAMC2 DNA present in skin biopsies taken from mice 72 hours after being administered intradermally or isolated from HSV LGA or vehicle control, as assessed by qPCR analysis.

[00157] FIG. 29C shows human LAMC2 transcript levels Petition 870260060403, dated 06 / 19 / 2026, page 62 / 300 / 237 present in skin biopsies taken from mice 72 hours after being administered intradermally or isolated from HSV LGA or vehicle control, as assessed by qRT-PCR analysis. For each condition in the qPCR and qRT-PCR analysis, data are presented as the mean of two replicates ± SEM.

[00158] FIG. 29D shows representative immunofluorescence images of human LAMC2 expression in skin biopsies taken from mice 72 hours after intradermal administration of HSV LGA isolate. A site that was administered intradermally alone was used as a negative control. DAPI staining was used to visualize nuclei; pKal staining was used to visualize mouse laminin-332. DESCRIPTION OF CUTTING

[00159] In some embodiments, this disclosure relates to recombinant nucleic acids (e.g., recombinant herpes viral genomes) encoding one or more cosmetic proteins and to the 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 in the skin, such as in, into, and / or through the skin (e.g., to the dermal ECM). In some embodiments, this disclosure relates to recombinant nucleic acids (e.g., recombinant herpes viral genomes) encoding one or more cosmetic proteins and to the uses of these recombinant nucleic acids in viruses (e.g., in a herpes virus), compositions, formulations, medicaments, and / or methods for augmenting, amplifying, and / or supplementing one or more dermal ECM proteins (e.g., one or more collagen proteins).In some embodiments, this disclosure refers to recombinant nucleic acids (e.g., recombinant herpes viral genomes) encoding one or more cosmetic proteins and their uses. Petition 870260060403, dated 06 / 19 / 2026, page 63 / 300 / 237 of these recombinant nucleic acids in viruses (e.g., in a herpes virus), compositions, formulations, medicaments and / or methods in an aesthetic context (e.g., to reduce one or more dermatological signs of aging). In some embodiments, the present disclosure refers to compositions comprising a recombinant herpes viral vector and methods comprising delivering the recombinant herpes viral vector into, to 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 that is expressed to achieve a cosmetic effect on mammalian skin.Heterologous nucleic acid can be delivered to a target mammalian 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 wherein the recombinant herpes viral vector is transported in, on, and / or through the epidermis, dermis, or subcutaneous tissue and introduced into the target skin cell where it is expressed. Without wishing to be limited by theory, it is believed that administration of one or more of the recombinant nucleic acids, viruses, and / or formulations described herein to an individual will enable increased production of functional dermal ECM proteins (e.g., human collagen) in the individual.Furthermore, without wishing to be limited by theory, it is believed that increasing, amplifying, 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 intensification, amplification, and / or supplementation of soft tissue; 2) the improvement of the quality, condition, and / or appearance of the skin; 3) the reduction of one or more superficial depressions in the skin (e.g., wrinkles); 4) the improvement of the texture, smoothness, elasticity, and / or tightness of the skin; and / or 5) the reduction of one or more dermatological signs of aging. Ultimately, without wishing to be limited by theory, it is believed that the acids... Petition 870260060403, dated 06 / 19 / 2026, page 64 / 300 / 237 recombinant nucleic acids, viruses, compositions and methods described herein provide a novel strategy for the delivery of functional cosmetic proteins in aesthetic settings.

[00160] The following description sets forth exemplary methods, parameters and the like. It should be recognized, however, that such description is not intended to be a limitation on the scope of the present disclosure, but rather is provided as a description of exemplary embodiments. General Techniques

[00161] 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 used methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual 3d edition (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Current Protocols in Molecular Biology (FM Ausubel, et al. eds., (2003)); the Methods in Enzymology series (Academic Press, Inc.); PCR 2: A Practical Approach (MJ MacPherson, BD Hames and GR Taylor eds. (1995)), Harlow and Lane, eds. (1988); Oligonucleotide Synthesis (MJ Gait, ed., 1984); Methods in Molecular Biology, Humana Press; Cell Biology: A Laboratory Notebook (JE Cellis, ed., 1998) Academic Press; Animal Cell Culture (RI Freshney, ed., 1987); Introduction to Cell and Tissue Culture (JP Mather and PERoberts, 1998) Plenum Press; Cell and Tissue Culture: Laboratory Procedures (A. Doyle, JB Griffiths and DG Newell, eds., 1993-8) J. Wiley and Sons; Gene Transfer Vectors for Mammalian Cells (JM Miller and MP Calos, eds., 1987); PCR: The Polymerase Chain Reaction, (Mullis et al., eds., 1994); Short Protocols in Molecular Biology (Wiley and Sons, 1999). Definitions

[00162] Before describing the invention in detail, it must be understood Petition 870260060403, dated 06 / 19 / 2026, p. 65 / 300 / 237, states that this invention is not limited to particular compositions or biological systems, which may, of course, vary. It should also be understood that the terminology used in this document is for the purpose of describing particular embodiments only and is not intended to be limiting.

[00163] As used in this document, the singular forms a / an, an / an and the / the include the referring plural forms, unless the context clearly indicates otherwise. Thus, for example, reference to a molecule optionally includes a combination of two or more such molecules and similar ones.

[00164] As used in this document, the term and / or includes any and all combinations of one or more of the associated listed items. For example, the term ae / or b may refer to aa alone, b alone, a or b, or aeb; the term a, be / or c may refer to aa alone, b alone, c alone, a or b, a or c, b or c, a, b, or c”, “aeb”, “aec”, “bec”, or “a, bec”; etc.

[00165] As used in this document, the term about refers to the usual error range for the respective value readily known to those skilled in this technical field. The reference to about a value or parameter here includes (and describes) variations of that which are directed to that value or parameter, by itself.

[00166] It is understood that the aspects and embodiments of the invention described in this document include comprising, consisting of, and essentially consisting of aspects and embodiments.

[00167] As used herein, the terms polynucleotide, nucleic acid sequence, nucleic acid, and variations thereof, shall be generic for polydeoxyribonucleotides (containing 2-deoxy-D-ribose), for polyribonucleotides (containing D-ribose), for any other type of polynucleotide that is an N-glycoside of a purine or pyrimidine base, and for other polymers containing non-nucleotide backbones, provided that Petition 870260060403, dated 06 / 19 / 2026, page 66 / 300 / 237 the polymers contain nucleobases in a configuration that allows base pairing and 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 by an analog and internucleotide modifications.

[00168] As used herein, a nucleic acid is “operatively linked” or “operatively bound” when it is placed in a functional relationship with another nucleic acid sequence. For example, a promoter or enhancer is operatively linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operatively linked to a coding sequence if it is positioned in such a way as to facilitate translation. Generally, operatively linked means that the DNA sequences being linked are contiguous.

[00169] As used in this document, the term vector refers to distinct elements that are used to introduce heterologous nucleic acids into cells for their expression or replication. An expression vector includes vectors capable of expressing nucleic acids that are operationally linked to regulatory sequences, such as promoter regions, that are capable of effecting the expression of such nucleic acids. Thus, an expression vector may refer to a DNA or RNA construct, such as a plasmid, a phage, a recombinant virus, or another vector that, upon introduction into an appropriate host cell, results in the expression of nucleic acids. Appropriate expression vectors are well known to those skilled in the art and include those that are replicable in eukaryotic cells and those that remain episomal or those that integrate into the host cell genome.

[00170] As used in this document, a reading structure Petition 870260060403, dated 06 / 19 / 2026, p. 67 / 300 / 237. An open or ORF refers to a continuous stretch of nucleic acids, DNA or RNA, that codes for a protein or polypeptide. Typically, nucleic acids comprise a translation initiation signal or start codon, such as ATG or AUG, and a stop codon.

[00171] As used in this document, 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 can affect post-transcriptional regulation, mRNA stability, and / or polynucleotide translation.

[00172] As used in this document, 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 respects, it confers a desired property to a cell into which it has been introduced or otherwise leads to a desired cosmetic, therapeutic, or diagnostic outcome.

[00173] The terms polypeptide, peptide, and protein are used interchangeably herein to refer to a polymer of amino acid residues.

[00174] As used in this document, a subject, host, or individual refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sporting, 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 modalities, the mammal is a human.

[00175] The term pharmaceutical formulation refers to a preparation whose form allows the biological activity of an active ingredient contained therein to be effective, and which does not contain additional components that are unacceptably toxic to a subject to whom the formulation will be administered. Pharmaceutically acceptable excipients (e.g., vehicles, additives) Petition 870260060403, dated 06 / 19 / 2026, p. 68 / 300 / 237, refers to those that can reasonably be administered to a subject to provide an effective dose of the active ingredient(s) employed.

[00176] As used in this document, cutaneous administration or administration via the cutaneous route refers to the delivery of a composition to a subject by contact, directly or otherwise, of a formulation comprising the composition to all (systemic) or a portion (topical) of a subject's skin. The term encompasses various routes of administration, including, but not limited to, topical and transdermal. Topical administration may be used as a means of delivering a composition to the epidermis or dermis of a subject, or to specific strata thereof.

[00177] As used herein, the term 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 slowing the rate of disease progression, improving or slowing the disease 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.

[00178] As used in this document, the term delaying the progression of a disease / disorder / defect refers to delaying, preventing, slowing down, retarding, stabilizing, and / or postponing the development of the disease / disorder / defect (e.g., wrinkles on the skin). This delay may vary over different periods of time depending on the history of the disease and / or the individual being treated. As is evident to one skilled in the art, a sufficient or significant delay may, in fact, encompass prevention, insofar as the individual does not develop the disease. Recombinant Nucleic Acids

[00179] Certain aspects of this disclosure relate to recombinant nucleic acids (for example, recombinant nucleic acids Petition 870260060403, dated 06 / 19 / 2026, page 69 / 300 / 237 isolated) 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 this 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 protein of the extracellular matrix (e.g., a collagen, elastin, fibronectin, laminin, fibrillin, etc.). In some forms, the cosmetic protein is collagen, elastin, fibronectin, or laminin protein (for example, human collagen, elastin, fibronectin, or laminin protein).

[00180] In some embodiments, the present disclosure refers 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 refers 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 COL3A1 (COL3) polypeptides) or human Collagen 7 (e.g., comprising three COL7A1 (COL7) polypeptides).In some embodiments, the present disclosure refers to recombinant nucleic acids comprising one or more polynucleotides encoding a heterotrimeric collagen (for example, a heterotrimeric human collagen, such as human Collagen 1 (for example, comprising two COL1A1 (COL1-1) polypeptides and one COL1A2 (COL1-2) polypeptide) or human Collagen 4 (for example, Petition 870260060403, dated 06 / 19 / 2026, page 70 / 300 / 237 comprising two COL4A1 (COL4-1) polypeptides and one COL4A2 (COL4-2) polypeptide. In some embodiments, this disclosure refers to recombinant nucleic acids comprising one or more polynucleotides encoding a homotrimeric collagen and a heterotrimeric collagen (for example, a recombinant nucleic acid comprising one or more polynucleotides encoding human Collagen 1 and human Collagen 3). In some embodiments, this disclosure refers to recombinant nucleic acids comprising one or more polynucleotides encoding human Collagen 1. In some embodiments, this disclosure refers to recombinant nucleic acids comprising one or more polynucleotides encoding human Collagen 3.

[00181] In some embodiments, this disclosure refers 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 essentially consists of or consists of the first cosmetic protein (e.g., essentially consists of or consists of a first human collagen protein). In some embodiments, this disclosure refers 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 another cosmetic protein (e.g., another human collagen protein).In some embodiments, the first and other cosmetic proteins (e.g., the first and other human collagen proteins) are the same. In some embodiments, the first and other cosmetic proteins (e.g., the first and other human collagen proteins) are different. In some embodiments, the linker polypeptide is a cleavable linker polypeptide. Petition 870260060403, dated 06 / 19 / 2026, page 71 / 300 / 237

[00182] In some embodiments, the present disclosure refers 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: an open first 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 the additional cosmetic proteins (e.g., the first and the additional human collagen proteins) are the same. In some embodiments, the first and the additional cosmetic proteins (e.g., the first and the additional human collagen proteins) are different.

[00183] In some embodiments, the present disclosure refers 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.

[00184] 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 recombinant nucleic acid is a herpes viral vector.In some embodiments, the recombinant nucleic acid is an amplicon of the herpes simplex virus. In some embodiments, the recombinant nucleic acid is an amplicon of the herpes virus. In some embodiments, the... Petition 870260060403, dated 06 / 19 / 2026, page 72 / 300 / 237 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 (HSV1) genome. Polynucleotides that encode cosmetic proteins. Polynucleotides that encode collagen proteins.

[00185] In some embodiments, the present disclosure refers 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) of any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, human collagen genes (see, for example, NCBI Gene IDs: 1277, 1278, 1281, 1282, 1284, 1291, 1294, 1308, etc.), mouse collagen genes (see, for example, NCBI Gene IDs: 12842, 12843, 12825, 12826, 12827, 12833, 12836, 12821, etc.), chimpanzee collagen genes (see, for example, NCBI Gene IDs: 104001053, 455117, 459815, 452689, etc.). 452661, 450204, 101056895, 101058306, etc.), mouse collagen genes (see for example, NCBI Gene IDs: 29393, 84352, 84032, 290905, 306628, 294337, 301012, 294027, etc.), rabbit collagen genes (see, for example, NCBI Gene IDs: 100347598, 100008997, 100009177, 100358256, 100358522, 100343947, 100356561, 100339335, etc.) etc. Methods for identifying homologs / orthologs of collagen genes from additional species are known to those skilled in the art, including, for example, the use of a nucleic acid sequence alignment program such as the BLAST®blastn suite. In some embodiments, a polynucleotide of the present disclosure comprises a sequence with 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. Petition 870260060403, dated 06 / 19 / 2026, p. 73 / 300 / 237 less than 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence of any of the collagen genes (and / or coding sequences thereof) described herein or known in the art.

[00186] 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, the use of a codon-optimized variant of the coding sequence of a collagen gene increases the stability and / or yield of heterologous expression (RNA and / or protein) of the encoded collagen protein in a target cell (such as an epidermal and / or dermal cell), compared with the stability and / or yield of heterologous expression of a corresponding wild-type sequence, not codon-optimized. 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, the methods described by Fath et al. (PLoS One. March 3, 2011;6(3): e17596).

[00187] In some embodiments, the present disclosure refers 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, for example, NCBI Gene ID: 1277; SEQ ID NO: 1), a COL1A2 gene (see, for example, NCBI Gene ID: 1278; SEQ ID NO: 3), a COL2A1 gene (see, for example, NCBI Gene ID: 1280), a COL3A1 gene (see, for example, NCBI Gene ID: 1281; SEQ ID NO: 5), a COL4A1 gene (see, for example, NCBI Gene ID: 1282; SEQ ID Petition 870260060403, dated 06 / 19 / 2026, p. 74 / 300 / 237 NO: 7), a COL4A2 gene (see, for example, NCBI Gene ID: 1284), a COL4A3 gene (see, for example, NCBI Gene ID: 1285), a COL4A4 gene (see, for example, NCBI Gene ID: 1286), a COL4A5 gene (see, for example, NCBI Gene ID: 1287), a COL4A6 gene (see, for example, NCBI Gene ID: 1288), a COL5A1 gene (see, for example, NCBI Gene ID: 1289), a COL5A2 gene (see, for example, NCBI Gene ID: 1290), a COL5A3 gene (see, for example, NCBI Gene ID: 50509), a COL6A1 gene (see, for example, NCBI Gene ID: 1291; SEQ ID NO: 9), a COL6A2 gene (see, for example, NCBI Gene ID: 1292), a COL6A3 gene (see, for example, NCBI Gene ID: 1293), a COL6A4 gene (see, for example, NCBI Gene ID: 344875), a COL6A5 gene (see, for example, NCBI Gene ID: 256076), a COL6A6 gene (see, for example, NCBI Gene ID: 131873), a COL7A1 gene (see, for example, NCBI Gene ID: 1294;SEQ ID NO: 10), a COL8A1 gene (see, for example, NCBI Gene ID: 1295), a COL9A1 gene (see, for example, NCBI Gene ID: 1297), a COL9A2 gene (see, for example, NCBI Gene ID: 1298), a COL9A3 gene (see, for example, NCBI Gene ID: 1299), a COL10A1 gene (see, for example, NCBI Gene ID: 1300), a COL11A1 gene (see, for example, NCBI Gene ID: 1301), a COL11A2 gene (see, for example, NCBI Gene ID: 1302), a COL12A1 gene (see, for example, NCBI Gene ID: 1303), a COL13A1 gene (see, for example, NCBI Gene ID: 1305), a COL14A1 gene (see, for example, NCBI Gene ID: 1306). ID: 7373), a COL15A1 gene (see, for example, NCBI Gene ID: 1306), a COL16A1 gene (see, for example, NCBI Gene ID: 1307), a COL17A1 gene (see, for example, NCBI Gene ID: 1308;SEQ ID NO: 12), a COL18A1 gene (see, for example, NCBI Gene ID: 80781), a COL19A1 gene (see, for example, NCBI Gene ID: 1310), a COL20A1 gene (see, for example, NCBI Gene ID: 57642), a COL21A1 gene (see, for example, NCBI Gene ID: 81578), a COL22A1 gene (see, for example, NCBI Gene ID: 169044), a COL23A1 gene (see, for example, NCBI Gene ID: 91522), a COL24A1 gene (see, for example, NCBI Gene ID: 255631), a COL25A1 gene (see, for example,; Petition 870260060403, dated 06 / 19 / 2026, p. 75 / 300 / 237 NCBI Gene ID: 84570), a COL26A1 gene (see, for example, NCBI Gene ID: 136227), a COL27A1 gene (see, for example, NCBI Gene ID: 85301), a COL28A1 gene (see, for example, 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 with 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 with the sequence of any of the human collagen genes (and / or coding sequences thereof) described herein or known in the art.

[00188] 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, the use of a codon-optimized variant of a human collagen gene increases the stability and / or yield of heterologous expression (RNA and / or protein) of human collagen in a target cell (such as a human keratinocyte or fibroblast), compared with the stability and / or yield of heterologous expression of a corresponding non-codon-optimized wild-type sequence.

[00189] 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 with 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 Petition 870260060403, dated 06 / 19 / 2026, p. 76 / 300 / 237 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with 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.

[00190] 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, the 3' truncation, or the 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 less 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 with 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 with nucleic acid sequence 1-4392 of SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a polynucleotide of the present disclosure comprises nucleic acid sequence 1-4392 of SEQ ID NO: 1 or SEQ ID NO: 2.

[00191] 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 with Petition 870260060403, dated 06 / 19 / 2026, page 77 / 300 / 237 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 with the sequence SEQ ID NO: 3 or SEQ ID NO: 4. In some embodiments, a polynucleotide of this disclosure comprises the sequence SEQ ID NO: 3 or SEQ ID NO: 4.

[00192] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 3 or SEQ ID NO: 4. In some embodiments, the 5' truncation, the 3' truncation, or fragment of the sequence with 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 less 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 with 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 with nucleic acid sequence 1-4098 of SEQ ID NO: 3 or SEQ ID NO: 4. In some embodiments, a polynucleotide of the present disclosure comprises nucleic acid sequence 1-4098 of SEQ ID NO: 3 or SEQ ID NO: 4.

[00193] In some embodiments, a polynucleotide of the present Petition 870260060403, dated 06 / 19 / 2026, p. 78 / 300 / 237, disclosure includes 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 with 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 with 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.

[00194] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 5 or SEQ ID NO: 6. In some embodiments, the 5' truncation, 3' truncation, or fragment of the sequence with 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 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 less 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 with 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 with nucleic acid sequence 1-4398 of SEQ ID NO: 5 or SEQ ID NO: 6. In some embodiments, a polynucleotide of the present disclosure... Petition 870260060403, dated 06 / 19 / 2026, p. 79 / 300 / 237, includes nucleic acid sequence 1-4398 of SEQ ID NO: 5 or SEQ ID NO: 6.

[00195] 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 with 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 with 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.

[00196] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 7 or SEQ ID NO: 8. In some embodiments, the 5' truncation, 3' truncation, or fragment of the sequence with 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 less 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 with 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. Petition 870260060403, dated 06 / 19 / 2026, p. 80 / 300 / 237 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with nucleic acid sequence 1-5007 of SEQ ID NO: 7 or SEQ ID NO: 8. In some embodiments, a polynucleotide of the present disclosure comprises nucleic acid sequence 1-5007 of SEQ ID NO: 7 or SEQ ID NO: 8.

[00197] 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 with 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 with 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.

[00198] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, the 5' truncation, the 3' truncation, or the fragment of the sequence with 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 less 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 with at least 75%, at least 80%, at least 85%, of the following nucleotides: Petition 870260060403, dated 06 / 19 / 2026, p. 81 / 300 / 237 less 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 with nucleic acid sequence 1-3084 of SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, a polynucleotide of the present disclosure comprises nucleic acid sequence 1-3084 of SEQ ID NO: 9 or SEQ ID NO: 10.

[00199] 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 with 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 with 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.

[00200] 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 SEQ ID NO: 11 or SEQ ID NO: 12 sequence 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, at least 5500, by the way. Petition 870260060403, dated 06 / 19 / 2026, p. 82 / 300 / 237 less than 6000, at least 6500, at least 7000, at least 7500, at least 8000, at least 8500, but less 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 with 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 with the acid sequence. nucleic acid sequence 1-8832 of SEQ ID NO: 11 or SEQ ID NO: 12. In some embodiments, a polynucleotide of the present disclosure comprises the nucleic acid sequence 1-8832 of SEQ ID NO: 11 or SEQ ID NO: 12.

[00201] 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 with 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 with 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.

[00202] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, the 5' truncation, 3' truncation, or fragment of the sequence with 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, or at least 10 ... Petition 870260060403, dated 06 / 19 / 2026, page. 83 / 300 / 237 less than 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 less 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 with 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 with nucleic acid sequence 1-4491 of SEQ ID NO: 13 or SEQ ID NO: 14.In some embodiments, a polynucleotide of the present disclosure comprises the nucleic acid sequence 1-4491 of SEQ ID NO: 13 or SEQ ID NO: 14.

[00203] In some embodiments, a polynucleotide of the present disclosure encoding one or more human collagen proteins (for example, a first human collagen protein, an additional 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 with 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, another 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. Petition 870260060403, dated 06 / 19 / 2026, page 84 / 300 / 237 Polynucleotides that encode fibronectin proteins

[00204] In some embodiments, the present disclosure refers 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) of 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, for example, NCBI Gene ID: 2335), a mouse fibronectin gene (see, for example, NCBI Gene ID: 14268), a chimpanzee fibronectin gene (see, for example, NCBI Gene ID: 459926), a rat fibronectin gene (see, for example, NCBI Gene ID: 25661), a rabbit fibronectin gene (see, for example, NCBI Gene ID: 100328589), etc. Methods for identifying homologs / orthologs of the fibronectin gene from additional species are known to those skilled in the art.In some embodiments, a polynucleotide of the present disclosure comprises a sequence with 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 with 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.

[00205] In some embodiments, the present disclosure refers to one or more polynucleotides (i.e., one or more first polynucleotides and / or one or more second polynucleotides) comprising the sequence of Petition 870260060403, dated 06 / 19 / 2026, p. 85 / 300 / 237 encoding 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-optimized variant thereof). In some embodiments, a polynucleotide of the present disclosure comprises a sequence with 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 with 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.

[00206] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 35 or SEQ ID NO: 36. In some embodiments, the 5' truncation, 3' truncation, or fragment of the sequence with 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 approximately 4500, at least approximately 5000, at least approximately 5500, at least approximately 6000, at least approximately 6500, at least approximately 7000, but less 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 with at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, and at least 90% of its components. Petition 870260060403, dated 06 / 19 / 2026, p. 86 / 300 / 237 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 with nucleic acid sequence 1-7431 of SEQ ID NO: 35 or SEQ ID NO: 36. In some embodiments, a polynucleotide of the present disclosure comprises nucleic acid sequence 1-7431 of SEQ ID NO: 35 or SEQ ID NO: 36. Polynucleotides that code for elastin proteins

[00207] In some embodiments, the present disclosure refers 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) of 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, for example, NCBI Gene ID: 2006), a mouse elastin gene (see, for example, NCBI Gene ID: 13717), a chimpanzee elastin gene (see, for example, NCBI Gene ID: 463943), a rat elastin gene (see, for example, NCBI Gene ID: 25043), a rabbit elastin gene (see, for example, NCBI Gene ID: 100344271), etc. Methods for identifying homologs / orthologs of the elastin gene from additional species are known to those skilled in the art.In some embodiments, a polynucleotide of the present disclosure comprises a sequence with 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 with 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... Petition 870260060403, dated 06 / 19 / 2026, p. 87 / 300 / 237 codon-optimized variant of any of the elastin genes (and / or coding sequences thereof) described herein or known in the art.

[00208] In some embodiments, the present disclosure refers 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 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 with 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 with the sequence of SEQ ID NO: 37 or SEQ ID NO: 38.In some embodiments, a polynucleotide of the present disclosure comprises the sequence SEQ ID NO: 37 or SEQ ID NO: 38.

[00209] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 37 or SEQ ID NO: 38. In some embodiments, the 5' truncation, the 3' truncation, or the fragment of the sequence with 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 less than 2361, consecutive nucleotides of SEQ ID NO: 37 or SEQ ID NO: 38. In some embodiments, Petition 870260060403, dated 06 / 19 / 2026, page. 88 / 300 / 237 a polynucleotide of the present disclosure comprises a sequence with 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 with the nucleic acid sequence 12358 of SEQ ID NO: 37 or SEQ ID NO: 38. In some embodiments, a polynucleotide of the present disclosure comprises the nucleic acid sequence 1-2358 of SEQ ID NO: 37 or SEQ ID NO: 38. Polynucleotides encoding lumican proteins

[00210] In some embodiments, the present disclosure refers to a recombinant nucleic acid comprising one or more polynucleotides comprising the coding sequence of a lumicane gene. The coding sequence of any lumicane gene (including any isoform thereof) of any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a human lumicane gene (see, for example, NCBI Gene ID: 4060), a mouse lumicane gene (see, for example, NCBI Gene ID: 17022), a chimpanzee lumicane gene (see, for example, NCBI Gene ID: 452119), a rat lumicane gene (see, for example, NCBI Gene ID: 81682), a rabbit lumicane gene (see, for example, NCBI Gene ID: 100008665), etc. Methods for identifying homologs / orthologs of the lumican gene from additional species are known to those skilled in the art.In some embodiments, a polynucleotide of the present disclosure comprises a sequence with 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. Petition 870260060403, dated 19 / 06 / 2026, p. 89 / 300 / 237 with 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.

[00211] In some embodiments, the present disclosure refers 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 with 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 with the sequence of SEQ ID NO: 39 or SEQ ID NO: 40.In some embodiments, a polynucleotide of the present disclosure comprises the sequence SEQ ID NO: 39 or SEQ ID NO: 40.

[00212] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 39 or SEQ ID NO: 40. In some embodiments, the 5' truncation, the 3' truncation, or the fragment of the sequence with 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 Petition 870260060403, dated 06 / 19 / 2026, p. 90 / 300 / 237 less 750, at least 1000, but less 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 with 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 with nucleic acid sequence 1-1014 of SEQ ID NO: 39 or SEQ ID NO: 40. In some embodiments, A polynucleotide of the present disclosure comprises the nucleic acid sequence 1-1014 of SEQ ID NO: 39 or SEQ ID NO: 40. Polynucleotides encoding vitronectin and vitronectin receptor proteins

[00213] In some embodiments, the present disclosure refers to a recombinant nucleic acid comprising one or more polynucleotides comprising the coding sequence of a vitronectin receptor gene or vitronectin.The coding sequence of any vitronectin or vitronectin receptor gene (including any isoform thereof) of any suitable species known in the art may be encoded by a polynucleotide of this disclosure, including, for example, a human vitronectin or vitronectin receptor gene (see, for example, NCBI Gene IDs: 7448 and 3685), a mouse vitronectin or vitronectin receptor gene (see, for example, NCBI Gene IDs: 22370 and 16410), a chimpanzee vitronectin or vitronectin receptor gene (see, for example, NCBI Gene IDs: 738261 and 459807), a rat vitronectin or vitronectin receptor gene (see, for example, NCBI Gene IDs: 29169 and 257645), a rabbit vitronectin or vitronectin receptor gene (see, for example, NCBI Gene IDs: 100009128 and 100008956), etc. The methods for identifying vitronectin homologs / orthologs or vitronectin receptor genes. Petition 870260060403, dated 06 / 19 / 2026, p. 91 / 300 / 237 additional species are known to those skilled in the art. In some embodiments, a polynucleotide of the present disclosure comprises a sequence with 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 with 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 either a vitronectin or vitronectin receptor gene (and / or coding sequences thereof) described herein or known in the art.

[00214] In some embodiments, the present disclosure refers 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 with 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 with the sequence of SEQ ID NO: 41 or SEQ ID NO: 42.In some embodiments, a polynucleotide of the present disclosure comprises the sequence SEQ ID NO: 41 or SEQ ID NO: 42.

[00215] In some embodiments, a polynucleotide of the present Petition 870260060403, dated 06 / 19 / 2026, p. 92 / 300 / 237 disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 41 or SEQ ID NO: 42. In some embodiments, the 5' truncation, the 3' truncation, or the fragment of the sequence with 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 less 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 with 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 with the nucleic acid sequence 1-1034 of SEQ ID NO: 41 or SEQ ID NO: 42. In some embodiments, a polynucleotide of the present disclosure comprises the nucleic acid sequence 1-1034 of SEQ ID NO: 41 or SEQ ID NO: 42. Polynucleotides encoding laminin proteins.

[00216] In some embodiments, the present disclosure refers 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) of any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, human laminin genes (see, for example, NCBI Gene IDs: 284217, 3908, 3909, 3910, 3911, 3912, 3913, 3914, 3915, 3918 and 10319), mouse laminin genes (see, for example, NCBI Gene IDs: 16774, 16780 and 16782), chimpanzee laminin genes (see, for example, NCBI Gene IDs: Petition 870260060403, dated 06 / 19 / 2026, p. 93 / 300 / 237 455339, 469668 and 457571), mouse laminin genes (see, for example, NCBI Gene IDs: 307582, 305078 and 192362), rabbit laminin genes (see, for example, NCBI Gene IDs: 100346886 and 100342905), etc. Methods for identifying homologs / orthologs of the laminin gene from additional species are known to those skilled 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 with 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 disclosure comprises a codon-optimized variant of any of the laminin genes (and / or coding sequences thereof) described herein or known in the art.

[00217] In some embodiments, the present disclosure refers 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 laminin gene, such as a human LAMA1 gene (see, for example, NCBI Gene ID: 284217), a human LAMA2 gene (see, for example, NCBI Gene ID: 3908), a human LAMA3 gene (see, for example, NCBI Gene ID: 3909), a human LAMA4 gene (see, for example, NCBI Gene ID: 3910), a human LAMA5 gene (see, for example, NCBI Gene ID: 3911), a human LAMB1 gene (see, for example, NCBI Gene ID: 3912), a human LAMB2 gene (see, for example, NCBI Gene ID: 3913), a human LAMB3 gene (see, for example, NCBI Gene ID: 3914), a human LAMC1 gene (see for example, NCBI Gene ID: 3915), a human LAMC2 gene (see for example, NCBI Gene ID: 3918) or a human LAMC3 gene Petition 870260060403, dated 06 / 19 / 2026, p. 94 / 300 / 237 (see, for example, NCBI Gene ID: 10319).

[00218] 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 with 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 with 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.

[00219] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 43 or SEQ ID NO: 44. In some embodiments, the 5' truncation, the 3' truncation, or the fragment of the sequence with 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 less 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 with 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. Petition 870260060403, dated 06 / 19 / 2026, p. 95 / 300 / 237 97%, at least 98%, at least 99%, or 100% sequence identity with nucleic acid sequence 1-5172 of SEQ ID NO: 43 or SEQ ID NO: 44. In some embodiments, a polynucleotide of the present disclosure comprises nucleic acid sequence 1-5172 of SEQ ID NO: 43 or SEQ ID NO: 44.

[00220] 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 with 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 with 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.

[00221] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 45 or SEQ ID NO: 46. In some embodiments, the 5' truncation, the 3' truncation, or the fragment of the sequence with 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 less 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 with at least 75%, at least 80%, Petition 870260060403, dated 06 / 19 / 2026, page 96 / 300 / 237 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 with nucleic acid sequence 1-3516 of SEQ ID NO: 45 or SEQ ID NO: 46. In some embodiments, a polynucleotide of the present disclosure comprises nucleic acid sequence 1-3516 of SEQ ID NO: 45 or SEQ ID NO: 46.

[00222] 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 with 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 with 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.

[00223] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 47 or SEQ ID NO: 48. In some embodiments, the 5' truncation, the 3' truncation, or the fragment of the sequence with 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 Petition 870260060403, dated 06 / 19 / 2026, page 97 / 300 / 237 3500, but less 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 with 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 with nucleic acid sequence 1-3579 of SEQ ID NO: 47 or SEQ ID NO: 48. In some embodiments, a polynucleotide of the present disclosure comprises the nucleic acid sequence 1-3579 of SEQ ID NO: 47 or SEQ ID NO: 48. Polynucleotides that encode neuromodulatory proteins

[00224] In some embodiments, the present disclosure refers 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) of any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a neuromodulator gene from Clostridium botulinum (see, for example, NCBI Gene IDs: 5185061 and 39483740), etc. Methods of identifying homologs / orthologs of the neuromodulator gene from additional species are known to those skilled in the art.In some embodiments, a polynucleotide of the present disclosure comprises a sequence with 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 with the sequence of any of the neuromodulator genes (and / or coding sequences of the...). Petition 870260060403, dated 06 / 19 / 2026, p. 98 / 300 / 237 same) 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.

[00225] In some embodiments, the present disclosure refers 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.

[00226] 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 sequence with 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 with 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.

[00227] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 49 or SEQ ID NO: 50. In some embodiments, the 5' truncation, the 3' truncation, or the fragment of the sequence with 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, Petition 870260060403, dated 06 / 19 / 2026, page. 99 / 300 / 237 at least 750, at least 1000, at least approximately 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, but less 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 with 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 with nucleic acid sequence 1-3888 of SEQ ID NO: 49 or SEQ ID NO: 50. In some embodiments, a polynucleotide of the present disclosure comprises nucleic acid sequence 1-3888 of SEQ ID NO: 49 or SEQ ID NO: 50.

[00228] 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 with 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 with 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.

[00229] In some embodiments, a polynucleotide of the present disclosure comprises a 5' truncation, a 3' truncation, or a fragment of the sequence with SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments, the 5' truncation, the 3' truncation, or the fragment of the sequence Petition 870260060403, dated 06 / 19 / 2026, page. 100 / 300 / 237 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 approximately 1250, at least 1500, at least 1750, at least 2000, at least 2500, at least 3000, at least 3500, but less than 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 with 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 with the nucleic acid sequence 1-3873 of SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments, a polynucleotide of the present disclosure comprises the nucleic acid sequence 1-3873 of SEQ ID NO: 51 or SEQ ID NO: 52. Polynucleotides that encode fibrillin proteins

[00230] In some embodiments, the present disclosure refers to a recombinant nucleic acid comprising one or more polynucleotides comprising the coding sequence of a fibrin gene. The coding sequence of any fibrillin gene (including any isoform thereof) of any suitable species known in the art may be encoded by a polynucleotide of this disclosure, including, for example, human fibrillin genes (see, for example, NCBI Gene IDs: 2200, 2201 and 84467), mouse fibrillin genes (see, for example, NCBI Gene IDs: 14118 and 14119), chimpanzee fibrillin genes (see, for example, NCBI Gene IDs: 453411, 471621 and 455669), rat fibrillin genes (see, for example, NCBI Gene IDs: 83727 and 689008), rabbit fibrillin genes (see, for example, Petition 870260060403, dated 06 / 19 / 2026, p. 101 / 300 / 237 NCBI Gene IDs: 100350931, 100357126 and 100359336), etc. Methods for identifying homologs / orthologs of the fibrillin gene from additional species are known to those skilled in the art. In some embodiments, a polynucleotide of the present disclosure comprises a sequence with 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 with 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.

[00231] In some embodiments, the present disclosure refers 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, for example, NCBI Gene ID: 2200), a human FBN2 gene (see, for example, NCBI Gene ID: 2201), or a human FBN3 gene (see, for example, NCBI Gene ID: 84467). Examples of polynucleotides

[00232] In some embodiments, a polynucleotide of the present disclosure encoding one or more cosmetic proteins (for example, a first cosmetic protein, an additional 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 less than 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity of Petition 870260060403, dated 19 / 06 / 2026, page 102 / 300 / 237 sequence with a nucleic acid sequence selected from SEQ ID NOS: 1-14 or 35-52. In some embodiments, a polynucleotide of the present disclosure encoding one or more cosmetic proteins (e.g., a first cosmetic protein, another cosmetic protein, an additional cosmetic protein and / or a second cosmetic protein) comprises a sequence selected from SEQ ID NOS: 1-14 or 35-52.

[00233] In some embodiments, a polynucleotide of the present disclosure encoding one or more cosmetic proteins (for example, a first cosmetic protein, an additional 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 with a nucleic acid sequence selected from SEQ ID NOS: 1-14, 35-38, or 43-48. In some embodiments, a polynucleotide of the present disclosure encoding one or more cosmetic proteins (for example, a first cosmetic protein, another cosmetic protein, an additional cosmetic protein, and / or a second cosmetic protein) comprises a sequence selected from SEQ ID NOS: 1-14, 35-38, or 4348.

[00234] A polynucleotide of the present disclosure encoding a cosmetic protein (e.g., a human collagen protein) may further encode 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., frame-encoded 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 tags Petition 870260060403, dated 19 / 06 / 2026, p. 103 / 300 / 237 Suitable polypeptide tags may include, but are not limited to, any combination of purification tags, such as hist tags, flag tags, maltose-binding protein and glutathione-S-transferase tags, detection tags, such as tags that can be detected photometrically (e.g., green fluorescent protein, red fluorescent protein, etc.) and tags that have 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 forms, the 5' and / or 3' UTRs increase the stability, localization, and / or translation efficiency of polynucleotides.In some modalities, 5' and / or 3' UTRs enhance the level and / or duration of protein expression. In some modalities, 5' and / or 3' UTRs include elements (e.g., one or more miRNA binding sites, etc.) that can block or reduce off-target expression (e.g., inhibit expression in specific cell types (e.g., neuronal cells), at specific times in the cell cycle, at specific developmental stages, etc.). In some modalities, 5' and / or 3' UTRs include elements (e.g., one or more miRNA binding sites, etc.) that can enhance the expression of cosmetic proteins in specific cell types (such as human keratinocytes and / or fibroblasts).

[00235] In some embodiments, a polynucleotide of the present disclosure encoding a cosmetic protein (e.g., a human collagen protein) is operationally 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 Petition 870260060403, dated 19 / 06 / 2026, p. 104 / 300 / 237 suitable enhancer(s) known in the art may be used, including, for example, enhancer sequences of mammalian genes (such as globin, elastase, albumin, α-fetoprotein, insulin and the like), enhancer sequences of a eukaryotic cell virus (such as SV40 enhancer on the late side of the origin of replication (bp 100-270), cytomegalovirus early promoter enhancer, polyome enhancer on the late side of the origin of replication, adenovirus enhancers and the like) and any combinations thereof. Any suitable isolator(s) known in the art may be used, including, for example, HSV chromatin boundary elements (CTRL / CTCF linkage / isolator) CTRL1 and / or CTRL2, chicken hypersensitive site isolator 4 (cHS4), human HNRPA2B1 — CBX3 ubiquitous chromatin opening element (UCOE),the scaffold / matrix attachment region (S / MAR) of 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 viral genomes (such as polyomavirus, avian poxvirus, adenovirus (such as Adenovirus 2), bovine papillomavirus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis B virus, simian virus 40 (SV40) and the like), promoters of heterologous mammalian genes (such as the actin promoter (e.g., the β-actin promoter), a ubiquitin promoter (e.g., a ubiquitin C (UbC) promoter), a phosphoglycerate kinase (PGK) promoter, an immunoglobulin promoter, heat shock promoters and the like), promoters of homologous mammalian genes (e.g., promoters of human native collagen, fibronectin, elastin,lumican, vitronectin, laminin and / or fibrillin), synthetic promoters (such as the CAGG promoter) and any combinations thereof, provided that such promoters are compatible with the cells, Petition 870260060403, dated 06 / 19 / 2026, p. 105 / 300 / 237 host cells. Regulatory sequences include those that direct the constitutive expression of a nucleotide sequence, as well as tissue-specific inducible and / or regulatory sequences.

[00236] In some embodiments, a polynucleotide of the present disclosure encoding a cosmetic protein (e.g., a human collagen protein) is operationally linked to one or more heterologous promoters. In some embodiments, one or more heterologous promoters are one or more of the constitutive promoters, tissue-specific promoters, temporal promoters, spatial promoters, inducible promoters, and repressible promoters. In some embodiments, one or more heterologous promoters are one or more of the immediate early promoter of human cytomegalovirus (HCMV), the human elongation factor-1 (EF1) promoter, the human β-actin promoter, the human UbC promoter, the 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 operationally linked to an HCMV promoter.

[00237] In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence (e.g., a transgene encoding) of a collagen alpha-1 (VII) chain polypeptide (COL7). In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence (e.g., a transgene encoding) of a Lysyl hydroxylase 3 (LH3) polypeptide. In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene encoding) a type I keratin cytoskeletal polypeptide 17 (KRT17). In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence (e.g., a transgene encoding) of a transglutaminase (TGM) polypeptide (e.g., a Petition 870260060403, dated 06 / 19 / 2026, page 106 / 300 / 237 human transglutaminase polypeptide, such as a human TGM1 polypeptide). In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence (e.g., a transgene coding) of a laminin beta-3 subunit polypeptide (LAMB3). In some embodiments, a polynucleotide of the present disclosure does not comprise the coding sequence of (e.g., a transgene coding) a collagen alpha-1 (VII) chain polypeptide, a lysyl hydroxylase 3 polypeptide, a type I keratin cytoskeletal polypeptide 17 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 coding) a collagen alpha-1 (VII) chain polypeptide, a lysyl hydroxylase 3 polypeptide, a type I keratin cytoskeletal 17 polypeptide, a transglutaminase (TGM) polypeptide (e.g., a human transglutaminase polypeptide, such as a human TGM1 polypeptide), a laminin beta-3 subunit (LAMB3) polypeptide (e.g., a human LamB3 polypeptide) and / or any chimeric polypeptide thereof. Cosmetic proteins Collagen proteins

[00238] In some embodiments, the present disclosure refers to one or more polynucleotides encoding a full-length collagen protein or any isoforms or portions thereof. Any collagen protein of any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, human collagen proteins (see, for example, UniProt Accession Numbers P02452, P08123, P02461, P02462, P08572, P12109, Q02388, Q9UMD9, etc.), mouse collagen proteins (see, for example, UniProt Accession Numbers P11087, Q01149, P08121, P02463, P08122, Petition 870260060403, dated 06 / 19 / 2026, p. 107 / 300 / 237 Q04857, Q63870, Q07563, etc.), chimpanzee collagen proteins (see, for example, UniProt accession numbers A0A2I3SM98, A0A2J8L483, H2QJ46, K7C8P4, K7C8W0, A0A2J8M8U9, H2QMJ5, H2Q2J4, etc.), rat collagen proteins (see, for example, UniProt accession numbers P02454, P02466, P13941, P02466, F1M6Q3, D3ZUL3, D3ZE04, D3ZE04, etc.), rat collagen proteins (see, for example, UniProt accession numbers G1T4A5, Q28668, G1T8J0, G1U9R7, (G1T548, G1T380, G1T548, etc.) etc. Methods for identifying collagen protein homologs / orthologs of additional species are known to those skilled in the art, including, for example, the use of an amino acid sequence alignment program such as the BLAST®blastn suite or OrthoDB.In some embodiments, a collagen polypeptide of the present disclosure comprises a sequence with 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 with the sequence of any of the collagen polypeptides described herein or known in the art.

[00239] In some embodiments, the present disclosure refers to one or more polynucleotides that encode a human collagen protein. Any suitable human collagen protein known in the art can be encoded by a polynucleotide of the present disclosure, including, for example, an alpha-1(I) collagen chain polypeptide (COL1-1) (see, for example, UniProt accession number P02452; SEQ ID NO: 15), an alpha-2(I) collagen chain polypeptide (COL1-2) (see, for example, UniProt accession number P08123; SEQ ID NO: 16), an alpha-1(II) collagen chain polypeptide (COL2) (see, for example, UniProt accession number P02458), an alpha-1(III) collagen chain polypeptide (COL3) (see, for example, UniProt accession number P2461; SEQ ID NO: 17), a Petition 870260060403, dated 06 / 19 / 2026, page. 108 / 300 / 237 collagen alpha-1(IV) chain polypeptide (COL4-1) (see, for example, UniProt accession number P02462; SEQ ID NO: 18), a collagen alpha-2(IV) chain polypeptide (COL4-2) (see, for example, UniProt accession number P08572), a collagen alpha-3(IV) chain polypeptide (COL4-3) (see, for example, UniProt accession number Q01955), a collagen alpha-4(IV) chain polypeptide (COL4-4) (see, for example, UniProt accession number P53420), a collagen alpha-5(IV) chain polypeptide (COL4-5) (see, for example, UniProt accession number 29400), a collagen alpha-6(IV) chain polypeptide (COL4-6) (see, for example, accession number UniProt Q14031), an alpha-1(V) chain collagen polypeptide (COL5-1) (see, for example, accession number UniProt P20908), an alpha-2(V) chain collagen polypeptide (COL5-2) (see, for example, accession number UniProt P05997),a collagen alpha-3(V) chain polypeptide (COL5-3) (see, for example, UniProt accession number P25940), a collagen alpha-1(VI) chain polypeptide (COL6-1) (see, for example, UniProt accession number P12109; SEQ ID NO: 19), a collagen alpha-2(VI) chain polypeptide (COL6-2) (see, for example, UniProt accession number P12110), a collagen alpha-3(VI) chain polypeptide (COL6-3) (see, for example, UniProt accession number P12111), a collagen alpha-4(VI) chain polypeptide (COL6-4), a collagen alpha-5(VI) chain polypeptide (COL6-5) (see, for example, UniProt accession number A8TX70), a collagen alpha-6(VI) chain polypeptide (COL6-6) (see, for example, UniProt accession number A6NMZ7), an alpha-1(VII) collagen chain polypeptide (COL7) (see, for example, UniProt accession number Q02388; SEQ ID NO: 20), an alpha-1(VIII) collagen chain polypeptide (COL8) (see, for example, UniProt accession number P27658),an alpha-1(IX) chain polypeptide of collagen (COL9-1) (see, for example, UniProt accession number P20849), an alpha-2(IX) chain polypeptide of collagen (COL9-2) (see, for example, UniProt accession number Q14055), an alpha-3(IX) chain polypeptide of, Petition 870260060403, dated 06 / 19 / 2026, page. 109 / 300 / 237 collagen (COL9-3) (see, for example, UniProt accession number Q14050), an alpha-1(X) chain polypeptide of collagen (COL10) (see, for example, UniProt accession number Q03692), an alpha-1(XI) chain polypeptide of collagen (COL11-1) (see, for example, UniProt accession number P12107), an alpha-2(XI) chain polypeptide of collagen (COL11-2) (see, for example, UniProt accession number P13942), an alpha-1(XII) chain polypeptide of collagen (COL12) (see, for example, UniProt accession number Q99715), an alpha-1(XIII) chain polypeptide of collagen (COL13) (see, for example, UniProt accession number Q5TAT6), a polypeptide of alpha-1(XIV) collagen chain (COL14) (see, for example, UniProt accession number Q05707), an alpha-1(XV) collagen chain polypeptide (COL15) (see, for example, UniProt accession number P39059), an alpha-1(XVI) collagen chain polypeptide (COL16) (see, for example,accession number UniProt Q07092), an alpha-1(XVII) collagen chain polypeptide (COL17) (see, for example, accession number UniProt Q9UMD9; SEQ ID NO: 21), an alpha-1(XVIII) collagen chain polypeptide (COL18) (see, for example, accession number UniProt P39060), an alpha-1(XIX) collagen chain polypeptide (COL19) (see, for example, accession number UniProt Q14993), an alpha-1(XX) collagen chain polypeptide (COL20) (see, for example, accession number UniProt Q9P218), an alpha-1(XXI) collagen chain polypeptide (COL21) (see, for example, accession number UniProt Q96P44), an alpha-1(XXII) collagen chain polypeptide (COL22) (see, for example, UniProt accession number Q8NFW1), an alpha-1(XXIII) collagen chain polypeptide (COL23) (see, for example, UniProt accession number Q86Y22), an alpha-1(XXIV) collagen chain polypeptide (COL24) (see, for example, UniProt accession number Q17RW2),an alpha-1(XXV) collagen chain polypeptide (COL25) (see, for example, accession number UniProt Q9BXS0), an alpha-1(XXVI) collagen chain polypeptide (COL26) (see, for example, accession number, Petition 870260060403, dated 06 / 19 / 2026, page 110 / 300 / 237 UniProt Q96A83), an alpha-1(XXVII) collagen chain polypeptide (COL27) (see, for example, accession number UniProt Q8IZC6), an alpha-1(XXVIII) collagen chain polypeptide (COL28) (see, for example, accession number UniProt Q2UY09), etc. In some embodiments, a polynucleotide of the present disclosure comprises a sequence with 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 for identifying additional human collagen or collagen-like polypeptide homologs / orthologs are known to those skilled in the art, including, for example, the use of an amino acid sequence alignment program such as the BLAST® blastp suite or OrthoDB.

[00240] 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 encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 15. In some embodiments, a polynucleotide encoding a human COL1-1 protein is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 15.

[00241] In some embodiments, a polynucleotide that codes for a Petition 870260060403, dated 06 / 19 / 2026, page. 111 / 300 / 237 protein COL1-1 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 less than 1464, consecutive amino acids of SEQ ID NO: 15.

[00242] 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 encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 16. In some embodiments, a polynucleotide encoding a human COL1-2 protein is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 16.

[00243] In some embodiments, a polynucleotide encoding a COL1-2 protein is a polynucleotide encoding 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 Petition 870260060403, dated 06 / 19 / 2026, page 112 / 300 100 / 237 200, 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 less than 1366, consecutive amino acids of SEQ ID NO: 16.

[00244] In some embodiments, a polynucleotide in the present disclosure encodes a human COL3 protein. In some embodiments, a polynucleotide encoding a COL3 protein is a polynucleotide encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 17. In some embodiments, a polynucleotide encoding a human COL3 protein is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 17.

[00245] In some embodiments, a polynucleotide encoding a COL3 protein is a polynucleotide encoding 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 less than 1466, consecutive amino acids of SEQ ID NO: 17.

[00246] In some embodiments, a polynucleotide of the present disclosure encodes a human COL4-1 protein. In some embodiments, Petition 870260060403, dated 06 / 19 / 2026, page 113 / 300 101 / 237 A polynucleotide encoding a COL4-1 protein is a polynucleotide encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 18. In some embodiments, a polynucleotide encoding a human COL4-1 protein is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 18.

[00247] In some embodiments, a polynucleotide encoding a COL4-1 protein is a polynucleotide encoding 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 less than 1669, consecutive amino acids of SEQ ID NO: 18.

[00248] 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 encoding a polypeptide comprising an amino acid sequence with 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 Petition 870260060403, dated 06 / 19 / 2026, page 114 / 300 102 / 237 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence of SEQ ID NO: 19. In some embodiments, a polynucleotide encoding a human COL6-1 protein is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 19.

[00249] In some embodiments, a polynucleotide encoding a COL6-1 protein is a polynucleotide encoding 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 less than 1028, consecutive amino acids of SEQ ID NO: 19.

[00250] In some embodiments, a polynucleotide in the present disclosure encodes a human COL7 protein. In some embodiments, a polynucleotide encoding a COL7 protein is a polynucleotide encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 20. In some embodiments, a polynucleotide encoding a human COL7 protein is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 20.

[00251] In some embodiments, a polynucleotide encoding a COL7 protein is a polynucleotide encoding an N-terminal truncation, Petition 870260060403, dated 06 / 19 / 2026, page 115 / 300 103 / 237 a C-terminal truncation or 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 less than 2944, consecutive amino acids of SEQ ID NO: 20.

[00252] In some embodiments, a polynucleotide in the present disclosure encodes a human COL17 protein. In some embodiments, a polynucleotide encoding a COL17 protein is a polynucleotide encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 21. In some embodiments, a polynucleotide encoding a human COL17 protein is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 21.

[00253] In some embodiments, a polynucleotide encoding a COL17 protein is a polynucleotide encoding 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, Petition 870260060403, dated 06 / 19 / 2026, page 116 / 300 104 / 237 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 less than 1497 consecutive amino acids of SEQ ID NO: 21.

[00254] In some embodiments, one or more human collagen proteins of the present disclosure (for example, a first human collagen protein, an additional 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: 1521. In some embodiments, one or more human collagen proteins of the present disclosure (for example, a first human collagen protein, another 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.

[00255] In some embodiments, one or more human collagen proteins of the present disclosure (for example, a first human collagen protein, an additional 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 Petition 870260060403, dated 19 / 06 / 2026, p. 117 / 300 105 / 237 17. In some embodiments, one or more human collagen proteins of the present disclosure (for example, a first human collagen protein, another human collagen protein, an additional human collagen protein and / or a second human collagen protein) comprise a selected sequence of SEQ ID NOS: 15-17. Fibronectin proteins

[00256] In some embodiments, the present disclosure refers to one or more polynucleotides encoding a full-length fibronectin protein or any isoforms or portions thereof. Any fibronectin protein of 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, for example, UniProt Accession Number P02751), a mouse fibronectin protein (see, for example, UniProt Accession Number P11276), a chimpanzee fibronectin protein (see, for example, UniProt Accession Number P11276), a rat fibronectin protein (see UniProt Accession Number P04937), a rabbit fibronectin protein (see UniProt Accession Number P04937), etc. Methods for identifying homologs / orthologs of the fibronectin protein from additional species are known to those skilled in the art.In some embodiments, a fibronectin protein of the present disclosure comprises a sequence with 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 with the sequence of any of the fibronectin proteins described herein or known in the art.

[00257] In some embodiments, a polynucleotide of the present disclosure encodes a human fibronectin protein. In some Petition 870260060403, dated 06 / 19 / 2026, page 118 / 300 106 / 237 embodiments, a polynucleotide encoding a fibronectin protein is a polynucleotide encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 53. In some embodiments, a polynucleotide encoding a human fibronectin protein is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 53.

[00258] In some embodiments, a A polynucleotide encoding a fibronectin protein is a polynucleotide encoding 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, by Less than 2300, at least 2400, but less than 2477, consecutive amino acids of SEQ ID NO: 53. Elastin and associated proteins.

[00259] Elastic fibers in the extracellular matrix provide elastic properties to the tissue. Elastic fibers generally contain two morphologically distinct components - mature elastin fibers and microfibrils that contain mainly fibrillin and are associated with other proteins, such as microfibril-associated glycoproteins (MAGPs), fibulins, and proteins. Petition 870260060403, dated 06 / 19 / 2026, page 119 / 300 107 / 237 located at the elastin-microfibril interface (EMILIN). Elastin and its soluble precursor, tropoelastin, are among the body's major structural proteins.

[00260] In some embodiments, this disclosure refers to one or more polynucleotides encoding an elastin or elastin-associated protein, including tropoelastin, fibrillin, microfibril-associated glycoprotein, fibulin, or a protein located at the elastin-microfibril interface. In some embodiments, this disclosure refers 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 can be encoded by a polynucleotide of the present disclosure, including, for example, a human elastin protein (see, for example, UniProt accession number P15502), a mouse elastin protein (see, for example, UniProt accession number P15502), a chimpanzee elastin protein (see, for example, UniProt accession number H2QUQ6), a rat elastin protein (see, for example, UniProt accession number Q99372), etc. Methods for identifying elastin protein homologs / orthologs from additional species are known to those skilled in the art.In some embodiments, an elastin protein of the present disclosure comprises a sequence with 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 with the sequence of any of the elastin proteins described herein or known in the art.

[00261] In some embodiments, a polynucleotide of the present disclosure encodes a human elastin protein. In some Petition 870260060403, dated 06 / 19 / 2026, pp. 120 / 300 108 / 237 embodiments, a polynucleotide encoding a human elastin protein is a polynucleotide encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 54. In some embodiments, a polynucleotide encoding a human elastin protein is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 54.

[00262] In some embodiments, a polynucleotide The polynucleotide that codes for an elastin protein is a polynucleotide that codes for an N-terminal truncation, a C-terminal truncation, or a fragment of the amino acid sequence with 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 less than 786, consecutive amino acids of SEQ ID NO: 54. Luminican proteins.

[00263] In some embodiments, the present disclosure refers to one or more polynucleotides encoding a full-length lumican protein or any isoforms or portions thereof. Any lumican protein of 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, for example, UniProt accession number P51884), a mouse lumican protein (see, for example, UniProt accession number P51885), a chimpanzee lumican protein (see, for example, UniProt accession number H2Q6L3), a Petition 870260060403, dated 06 / 19 / 2026, page 121 / 300 109 / 237 rat lumican protein (see UniProt accession number H2Q6L3), a rabbit lumican protein (see, for example, UniProt accession number O46379), etc. Methods for identifying homologs / orthologs of lumican protein from additional species are known to those skilled in the art. In some embodiments, a lumican protein of the present disclosure comprises a sequence with 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 with the sequence of any of the lumican proteins described herein or known in the art.

[00264] 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 encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 55. In some embodiments, a polynucleotide encoding a human lumican protein is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 55.

[00265] In some embodiments, a polynucleotide encoding a lumican protein is a polynucleotide encoding 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 Petition 870260060403, dated 06 / 19 / 2026, page 122 / 300 110 / 237 terminals 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 less than 338, consecutive amino acids of SEQ ID NO: 55. Vitronectin and vitronectin receptor proteins

[00266] In some embodiments, the present disclosure refers to one or more polynucleotides encoding a full-length vitronectin protein and vitronectin receptor or any isoforms or portions thereof.Any vitronectin protein or vitronectin receptor of any suitable species known in the art may be encoded by a polynucleotide of this disclosure, including, for example, a human vitronectin protein or vitronectin receptor (see, for example, UniProt accession numbers P04004 and P06756), a mouse vitronectin protein or vitronectin receptor (see, for example, UniProt accession numbers P29788 and P43406), a chimpanzee vitronectin protein or vitronectin receptor (see, for example, UniProt accession numbers H2QCH3 and H2R6C3), a rat vitronectin protein or vitronectin receptor (see, for example, UniProt accession number Q7TQ11), a rabbit vitronectin protein or vitronectin receptor (see, for example, UniProt accession number P22458), etc.Methods for identifying vitronectin homologs / orthologs or vitronectin receptor protein from additional species are known to those skilled in the art. In some embodiments, a vitronectin protein and vitronectin receptor of the present disclosure comprises a sequence with 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%, by. Petition 870260060403, dated 06 / 19 / 2026, p. 123 / 300 111 / 237 less than 99%, or 100% sequence identity with the sequence of any of the vitronectin proteins and vitronectin receptor described herein or known in the art.

[00267] In some embodiments, a polynucleotide in the present disclosure encodes a human vitronectin protein. In some embodiments, a polynucleotide encoding a human vitronectin protein is a polynucleotide encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 56. In some embodiments, a polynucleotide encoding a human vitronectin protein is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 56.

[00268] In some embodiments, a polynucleotide encoding a vitronectin protein is a polynucleotide encoding 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 less than 478, consecutive amino acids of SEQ ID NO: 56. Laminin proteins

[00269] In some embodiments, the present disclosure refers to one or more polynucleotides encoding a full-length laminin protein or any isoforms or portions thereof. Any Petition 870260060403, dated 06 / 19 / 2026, p. 124 / 300 112 / 237 laminin protein of 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, for example, UniProt accession numbers P25391, P24043, Q16787, Q16363, O15230, P07942, P55268, Q13751, P11047, Q13753 and Q9Y6N6), a mouse laminin protein (see, for example, UniProt accession numbers Q61789, Q61087 and Q61092), a chimpanzee laminin protein (see, for example, UniProt accession numbers H2QEC7, H2R041 and H2Q0R2), a rat laminin protein (see, for example, accession numbers UniProt D3ZN05, F1LPI5 and F1LRH4), a rabbit laminin protein (see, for example, accession numbers UniProt G1SY40 and A0A0B5JSH0), etc. Methods for identifying homologs / orthologs of laminin protein from additional species are known to those skilled in the art.In some embodiments, a laminin protein of the present disclosure comprises a sequence with 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 with the sequence of any of the laminin proteins described herein or known in the art.

[00270] In some embodiments, a polynucleotide of the present disclosure encodes a human laminin protein, such as a human laminin alpha-1 subunit (LamA1) polypeptide (see, for example, UniProt accession number P25391), a human laminin alpha-2 subunit (LamA2) polypeptide (see, for example, UniProt accession number P24043), a human laminin alpha-3 subunit (LamA3) polypeptide (see, for example, UniProt accession number Q16787), a human laminin alpha-4 subunit (LamA4) polypeptide (see, for example, UniProt accession number Q16363), a human laminin alpha-5 subunit polypeptide Petition 870260060403, dated 06 / 19 / 2026, page 125 / 300 113 / 237 (LamA5) (see, for example, UniProt accession number O15230), a human laminin beta-1 subunit polypeptide (LamB1) (see, for example, UniProt accession number P07942), a human laminin beta-2 subunit polypeptide (LamB2) (see, for example, UniProt accession number P55268), a human laminin beta-3 subunit polypeptide (LamB3) (see, for example, UniProt accession number Q13751), a human laminin gamma-1 subunit polypeptide (LamC1) (see, for example, UniProt accession number P11047), a human laminin gamma-2 subunit polypeptide (LamC2) (see, for example, UniProt accession number Q13753), a polypeptide of human laminin gamma-3 subunit (LamC3) (see, for example, UniProt accession number Q9Y6N6), etc.

[00271] 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 encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 57. In some embodiments, a polynucleotide encoding a human LamA3 polypeptide is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 57.

[00272] In some embodiments, a polynucleotide encoding a human LamA3 polypeptide is a polynucleotide encoding 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, Petition 870260060403, dated 06 / 19 / 2026, page 126 / 300 114 / 237 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 less than 3333, consecutive amino acids of SEQ ID NO: 57.

[00273] 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 encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 58. In some embodiments, a polynucleotide encoding a human LamB3 polypeptide is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 58.

[00274] In some embodiments, a polynucleotide encoding a human LamB3 polypeptide is a polynucleotide encoding 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, by Petition 870260060403, dated 06 / 19 / 2026, page 127 / 300 115 / 237 less than 1100, but less than 1172, consecutive amino acids of SEQ ID NO: 58.

[00275] 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 encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 59. In some embodiments, a polynucleotide encoding a human LamC2 polypeptide is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 59.

[00276] In some embodiments, a polynucleotide encoding a human LamC2 polypeptide is a polynucleotide encoding 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 less than 1193, consecutive amino acids of SEQ ID NO: 59. Neuromodulatory proteins

[00277] In some embodiments, the present disclosure refers to one or more polynucleotides encoding a neuromodulatory protein of Petition 870260060403, dated 06 / 19 / 2026, page 128 / 300 116 / 237 total length or any isoforms or portions thereof. Any neuromodulatory protein of any suitable species known in the art may be encoded by a polynucleotide of the present disclosure, including, for example, a protein from Clostridium botulinum (see, for example, UniProt accession numbers P0DPI0, Q45894, P0DPI1, P10844 and B1INP5), etc. Methods of identifying homologs / orthologs of the neuromodulatory protein from additional species are known to those skilled in the art.In some embodiments, a neuromodulator protein of the present disclosure comprises a sequence with 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 with the sequence of any of the neuromodulator proteins described herein or known in the art.

[00278] In some embodiments, a polynucleotide in the present disclosure encodes a neuromodulatory protein from Clostridium botulinum.

[00279] In some embodiments, a polynucleotide of the present disclosure encodes a Clostridium botulinum type A neurotoxin protein. In some embodiments, a polynucleotide encoding a Clostridium botulinum type A neurotoxin protein is a polynucleotide encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 60. In some embodiments, a polynucleotide encoding a Clostridium botulinum neurotoxin protein botulinum toxin type A is a polynucleotide that codes for a Petition 870260060403, dated 06 / 19 / 2026, pp. 129 / 300 117 / 237 polypeptide comprising the amino acid sequence of SEQ ID NO: 60. In some embodiments, a Clostridium botulinum type A neurotoxin protein of the present disclosure comprises an alanine-to-valine mutation at a position corresponding to position 27 of SEQ ID NO: 60.

[00280] In some embodiments, a polynucleotide encoding a Clostridium botulinum neurotoxin type A protein is a polynucleotide encoding 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 less than 1296, consecutive amino acids of SEQ ID NO: 60.

[00281] 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 encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 61. In some embodiments, a polynucleotide encoding a Clostridium neurotoxin type B protein botulinum nucleotide type B is a polynucleotide that codes for a polypeptide comprising the amino acid sequence SEQ ID NO: 61. Petition 870260060403, dated 06 / 19 / 2026, pp. 130 / 300 118 / 237

[00282] In some embodiments, a polynucleotide encoding a Clostridium botulinum neurotoxin type B protein is a polynucleotide encoding 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 less than 1291, consecutive amino acids from SEQ ID NO: 61. Fibrillin proteins

[00283] In some embodiments, the present disclosure refers to one or more polynucleotides encoding a full-length fibrillin protein or any isoforms or portions thereof. Any fibrillin protein of 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, for example, UniProt accession numbers P35555, P35556 and Q75N90), a mouse fibrillin protein (see, for example, UniProt accession numbers Q61554 and Q61555), a chimpanzee fibrillin protein (see, for example, UniProt accession numbers A0A2I3RTE4 and K7CZX0), a rat fibrillin protein (see, for example, UniProt accession numbers G3V9M6 and F1M5Q4), a rabbit fibrillin protein (see, for example, UniProt accession numbers G1SKM2, G1SUS5 and G1T1H4), etc.Methods for identifying homologs / orthologs of the fibrillin protein from additional species are known to those skilled in the art. In some embodiments, a fibrillin protein of the present disclosure comprises a sequence with at least 75%, at least 80%, at least 85%, at least 86%, by. Petition 870260060403, dated 06 / 19 / 2026, page 131 / 300 119 / 237 less than 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 with the sequence of any of the fibrillin proteins described herein or known in the art.

[00284] In some embodiments, a polynucleotide of the present disclosure encodes a human fibrillin protein.

[00285] In some embodiments, a polynucleotide of the present disclosure encodes a human fibrillin protein 1. In some embodiments, a polynucleotide encoding a human fibrillin protein 1 is a polynucleotide encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 62. In some embodiments, a polynucleotide encoding a human fibrillin protein 1 is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 62.

[00286] In some embodiments, a polynucleotide encoding a human fibrillin protein 1 is a polynucleotide encoding 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, Petition 870260060403, dated 06 / 19 / 2026, page 132 / 300 120 / 237 at least 2000, at least 2250, at least 2500, at least 2750, but less than 2871, consecutive amino acids of SEQ ID NO: 62.

[00287] In some embodiments, a polynucleotide of the present disclosure encodes a human fibrillin protein 2. In some embodiments, a polynucleotide encoding a human fibrillin protein 2 is a polynucleotide encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 63. In some embodiments, a polynucleotide encoding a human fibrillin protein 2 is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 63.

[00288] In some embodiments, a polynucleotide encoding a human fibrillin 2 protein is a polynucleotide encoding 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 less than 2912, consecutive amino acids of SEQ ID NO: 63.

[00289] In some embodiments, a polynucleotide of the present disclosure encodes a human fibrillin protein 3. In some embodiments, a polynucleotide encoding a fibrillin protein Petition 870260060403, dated 06 / 19 / 2026, page 133 / 300 121 / 237 human 3 is a polynucleotide encoding a polypeptide comprising an amino acid sequence with 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 with the sequence of SEQ ID NO: 64. In some embodiments, a polynucleotide encoding a human fibrillin protein 3 is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 64.

[00290] In some embodiments, a polynucleotide encoding a human fibrillin protein 3 is a polynucleotide encoding 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 less than 2809, consecutive amino acids of SEQ ID NO: 64. Examples of cosmetic polypeptides

[00291] In some embodiments, one or more cosmetic proteins of the present disclosure (for example, a first cosmetic protein, another 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 Petition 870260060403, dated 06 / 19 / 2026, page 134 / 300 122 / 237 100% sequence identity with a selected amino acid sequence from SEQ ID NOS: 15-21 or 53-64. In some embodiments, one or more cosmetic proteins of the present disclosure (e.g., a first cosmetic protein, another cosmetic protein, an additional cosmetic protein, and / or a second cosmetic protein) comprises a selected sequence from SEQ ID NOS: 15-21 or 53-64.

[00292] In some embodiments, one or more cosmetic proteins of the present disclosure (for example, a first cosmetic protein, another 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 with 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 (for example, a first cosmetic protein, another cosmetic protein, an additional cosmetic protein and / or a second cosmetic protein) comprises a sequence selected from SEQ ID NOS: 15-21, 53-54, or 5759. First polynucleotides

[00293] In some embodiments, the present disclosure refers 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, etc. In some embodiments, the first cosmetic protein is a Petition 870260060403, dated 06 / 19 / 2026, page 135 / 300 123 / 237 structural protein of the extracellular matrix (e.g., collagen, elastin, fibronectin, laminin, fibrillin, etc.). In some embodiments, the first cosmetic protein is a collagen, elastin, fibronectin, or laminin protein (e.g., human collagen, elastin, fibronectin, or laminin protein).

[00294] In some embodiments, a recombinant nucleic acid of this disclosure comprises one copy of the first polynucleotide. In some embodiments, a recombinant nucleic acid of this 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 this disclosure comprises two copies of the first polynucleotide.

[00295] 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 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, 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 modalities, the first human collagen protein is COL3. In some modalities, the first human collagen protein is COL4-1. In some modalities, the first human collagen protein is COL4-2. Petition 870260060403, dated 06 / 19 / 2026, page 136 / 300 124 / 237 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.

[00296] 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

[00297] 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 another cosmetic protein. In some embodiments, the chimeric polypeptide comprises a linker polypeptide that links the first cosmetic protein and another cosmetic protein. In some embodiments, the chimeric polypeptide comprises, from the n-terminus to the c-terminus, the first cosmetic protein – the linker polypeptide – and another cosmetic protein. The first and / or other 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 first and / or other cosmetic protein is a structural protein of the extracellular matrix (e.g., collagen, elastin, fibronectin, laminin, fibrillin, etc.). In some embodiments, the first and / or other cosmetic protein is a collagen, elastin, fibronectin, or laminin protein (e.g., human collagen, elastin, fibronectin, or laminin protein). In some embodiments, the first and other proteins. Petition 870260060403, dated 06 / 19 / 2026, page 137 / 300 125 / 237 cosmetics are the same. In some forms, the first and other cosmetic proteins are different.

[00298] In some embodiments, the linking polypeptide is a cleavable linking polypeptide. Any cleavable linking polypeptide known in the art can be used in the chimeric polypeptides of the present disclosure, including, for example, a T2A linker, a P2A linker, an E2A linker, and an F2A linker, etc. In other embodiments, the linking polypeptide is a T2A linking polypeptide. An exemplary nucleic acid sequence encoding a T2A linking polypeptide is provided as SEQ ID NO: 24. An exemplary amino acid sequence of a T2A linking polypeptide is provided as SEQ ID NO: 28. In other embodiments, the linking polypeptide is a P2A linking polypeptide. An exemplary nucleic acid sequence encoding a P2A-binding polypeptide is provided as SEQ ID NO: 25. An exemplary amino acid sequence of a P2A-binding polypeptide is provided as SEQ ID NO: 29. In other embodiments, the binding polypeptide is an E2A-binding polypeptide.An exemplary nucleic acid sequence encoding an E2A-binding polypeptide is provided as SEQ ID NO: 26. An exemplary amino acid sequence of an E2A-binding polypeptide is provided as SEQ ID NO: 30. In other embodiments, the binding polypeptide is an F2A-binding polypeptide. An exemplary nucleic acid sequence encoding an F2A-binding polypeptide is provided as SEQ ID NO: 27. An exemplary amino acid sequence of an F2A-binding polypeptide is provided as SEQ ID NO: 31.

[00299] In some embodiments, the linker polypeptide comprises a sequence with 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 with an amino acid sequence. Petition 870260060403, dated 06 / 19 / 2026, page 138 / 300 126 / 237 selected from SEQ ID NOS: 28-31. In some embodiments, the linker polypeptide comprises a sequence selected from SEQ ID NOS: 28-31.

[00300] In some embodiments, the first cosmetic protein is a first collagen protein (e.g., a first human collagen protein) and the other cosmetic protein is another collagen protein (e.g., another human collagen protein). An exemplary nucleic acid sequence encoding a chimeric polypeptide comprising a first human collagen protein, a linker polypeptide, and another human collagen protein is provided as SEQ ID NO: 32.

[00301] In some embodiments, the first cosmetic protein is a first human collagen protein and the other cosmetic protein is another human collagen protein. The other human collagen protein may be any of the human collagen proteins described herein or known in the art. In some embodiments, the other 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, COL93, COL10, 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 other human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL42, COL6-1, COL7, or COL17. In some embodiments, the other human collagen protein is COL1-1. In some embodiments, the other human collagen protein is COL1-2.In some embodiments, the other human collagen protein is COL3. In some embodiments, the other human collagen protein is COL4-1. In some embodiments, the other human collagen protein is COL4-2. In some embodiments, the other human collagen protein is COL6-1. In some embodiments, the other protein... Petition 870260060403, dated 06 / 19 / 2026, page 139 / 300 127 / 237 human collagen is COL7. In some embodiments, the other human collagen protein is not COL7. In some embodiments, the other 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.

[00302] In some embodiments, the first human collagen protein is COL1-1 and the other 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 other human collagen protein is COL1-2. In some embodiments, the first human collagen protein is COL1-1 and the other human collagen protein is COL3.

[00303] In some embodiments, the first human collagen protein is COL1-2 and the other 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 COL1-2 and the other human collagen protein is COL1-1.

[00304] In some embodiments, the first human collagen protein is COL3 and the other human collagen protein is selected from COL11, COL1-2, COL4-1, COL4-2, COL6-1, COL7 or COL17.

[00305] In some embodiments, the first human collagen protein is COL4-1 and the other human collagen protein is COL1-1, COL1-2, COL3, COL4-2, COL6-1, COL7, or COL17. In some embodiments, the first human collagen protein is COL4-1 and the other human collagen protein is COL4-2.

[00306] In some embodiments, the first human collagen protein is COL6-1 and the other human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL7 or COL17. Petition 870260060403, dated 06 / 19 / 2026, pp. 140 / 300 128 / 237

[00307] In some embodiments, the first human collagen protein is COL7 and the other human collagen protein is COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1 or COL17.

[00308] In some embodiments, the first human collagen protein is COL17 and the other human collagen protein is COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1 or COL7.

[00309] In some embodiments, the first cosmetic protein is a first laminin protein (e.g., a first human laminin protein) and the other cosmetic protein is an additional laminin protein (e.g., an additional human laminin protein). In some embodiments, the first cosmetic protein is a first human laminin protein and the other cosmetic protein is an additional human laminin protein. The other 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 other human laminin protein is a human LamB3 polypeptide. In some embodiments, the first human laminin protein is a human LamA3 polypeptide and the other human laminin protein is a human LamC2 polypeptide.In some embodiments, the first human laminin protein is a human LamB3 polypeptide and the other human laminin protein is a human LamC2 polypeptide.

[00310] In some embodiments, the first polynucleotide encodes a monocistronic mRNA. In some embodiments, the monocistronic mRNA comprises an open reading frame (ORF) that encodes the first polypeptide.

[00311] In some embodiments, the first polynucleotide encodes a polycistronic mRNA. In some embodiments, the polycistronic mRNA comprises an open reading frame (ORF) that encodes the first Petition 870260060403, dated 06 / 19 / 2026, page 141 / 300 129 / 237 polypeptide. polycistronic mRNA

[00312] 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) that separates the first ORF and the second ORF. In some embodiments, the polycistronic mRNA comprises, from 5' to 3', the first ORF encoding the first polypeptide – the IRES – and the second ORF encoding the additional cosmetic protein. The first polypeptide can be any of the first polypeptides described herein.The additional cosmetic protein can 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 protein of the extracellular matrix (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).

[00313] Any suitable IRES known in the art may be used in the polycistronic mRNAs of the present disclosure, including, for example, a virus-derived IRES (e.g., an IRES derived from a poliovirus, rhinovirus, encephalomyocarditis virus (EMCV), foot-and-mouth disease virus, virus of Petition 870260060403, dated 06 / 19 / 2026, p. 142 / 300 130 / 237 hepatitis C, classical swine fever virus, Roux-en-Y 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 transcript factor mRNAs, such as antennapedia, ultrabithorax, and NF-κB repression factor; an IRES derived from oncogene mRNAs, such as c-myc, pim-1, and p58PITSLRE protein kinase, etc.), a synthetic IRES (e.g., a CP148 IRES), and others (see, for example, 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 modalities, the IRES is an IRES CP148.An exemplary nucleic acid sequence encoding an IRES CP148 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.

[00314] In some embodiments, the nucleic acid sequence encoding IRES comprises a sequence with 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 with a nucleic acid sequence selected from SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments, the nucleic acid sequence encoding IRES comprises the sequence from SEQ ID NO: 22 or SEQ ID NO: 23.

[00315] 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. Petition 870260060403, dated 06 / 19 / 2026, page 143 / 300 131 / 237 (for example, an additional human collagen protein). An example of nucleic acid encoding a polycistronic mRNA comprising a first ORF, an IRES, and a 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, additional human collagen protein is selected from COL11, 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, or COL28. In some embodiments, the first additional collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL61, 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.

[00316] 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 Petition 870260060403, dated 06 / 19 / 2026, page 144 / 300 In 132 / 237 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.

[00317] 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.

[00318] 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.

[00319] 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, COL6-1, COL7, or COL17. In some embodiments, the first human collagen protein is COL4-1 and the additional human collagen protein is COL4-2.

[00320] 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.

[00321] In some embodiments, the first human collagen protein is COL7 and the additional human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1 or COL17.

[00322] In some embodiments, the first human collagen protein is COL17 and the additional human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1 or COL7.

[00323] 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. Petition 870260060403, dated 06 / 19 / 2026, page 145 / 300 133 / 237 (for example, an additional human collagen protein).

[00324] 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

[00325] In some embodiments, the present disclosure refers to a recombinant nucleic acid that further comprises 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 protein of the extracellular matrix (e.g., collagen, elastin, fibronectin, laminin, fibrillin, etc.). In some embodiments, the second cosmetic protein is a collagen, elastin, fibronectin, or laminin protein. Petition 870260060403, dated 06 / 19 / 2026, page 146 / 300 134 / 237 (for example, human collagen, 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 (for example, 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.

[00326] 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, COL93, COL10, 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, COL61, 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 modalities, the second human collagen protein is COL3. In some modalities, the second human collagen protein is COL4-1. In some modalities, the second human collagen protein is COL4-2. In some modalities, the second human collagen protein is COL6-1. In some modalities, the second collagen protein... Petition 870260060403, dated 06 / 19 / 2026, page 147 / 300 135 / 237 human collagen is COL7. In some embodiments, the second human collagen protein is not COL7. In some embodiments, the second human collagen protein is COL17.

[00327] 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.

[00328] 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, or COL17. In some embodiments, the first human collagen protein is COL1-1 and the second human collagen protein is COL1-2. In some embodiments, the first human collagen protein is COL1-1 and the second human collagen protein is COL3.

[00329] In some embodiments, the first human collagen protein is COL1-2 and the second 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 second human collagen protein is COL1-1.

[00330] In some embodiments, the first human collagen protein is COL3 and the second human collagen protein is selected from COL1-1, COL1-2, COL4-1, COL4-2, COL6-1, COL7 or COL17. Petition 870260060403, dated 06 / 19 / 2026, page 148 / 300 136 / 237

[00331] In some embodiments, the first human collagen protein is COL4-1 and the second human collagen protein is selected from COL1-2, COL1-2, COL3, COL4-2, COL6-1, COL7, or COL17. In some embodiments, the first human collagen protein is COL4-1 and the second human collagen protein is COL4-2.

[00332] In some embodiments, the first human collagen protein is COL6-1 and the second human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL7 or COL17.

[00333] In some embodiments, the first human collagen protein is COL7 and the second human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1 or COL17.

[00334] In some embodiments, the first human collagen protein is COL17 and the second human collagen protein is selected from COL1-1, COL1-2, COL3, COL4-1, COL4-2, COL6-1 or COL7.

[00335] In some embodiments, the first polynucleotide encodes a first laminin protein (e.g., a first human laminin protein) and the second polynucleotide encodes a second laminin protein (e.g., a second human laminin protein). In some embodiments, the first polynucleotide encodes a first human laminin polypeptide and the second polynucleotide encodes a second human laminin protein. The second 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 second human laminin protein is a human LamB3 polypeptide. In some embodiments, the first human laminin protein is a human LamA3 polypeptide and the second human laminin protein is a human LamC2 polypeptide.In some embodiments, the first human laminin protein is a human LamB3 polypeptide and the second laminin protein. Petition 870260060403, dated 06 / 19 / 2026, page 149 / 300 137 / 237 human is a human LamC2 polypeptide Recombinant nucleic acids

[00336] In some embodiments, the present disclosure refers to recombinant nucleic acids comprising any one or more of the polynucleotides described herein. In some embodiments, the recombinant nucleic acid comprises one copy of the first polynucleotide. In some embodiments, the recombinant nucleic acid comprises two copies of the first polynucleotide. In some embodiments, the recombinant nucleic acid comprises one copy of the first polynucleotide and one copy of the second polynucleotide. In some embodiments, the recombinant nucleic acid comprises one copy of the first polynucleotide and two copies of the second polynucleotide. In some embodiments, the recombinant nucleic acid comprises two copies of the first polynucleotide and one copy of the second polynucleotide. In some embodiments, the recombinant nucleic acid comprises two copies of the first polynucleotide and two copies of the second polynucleotide.

[00337] In some embodiments, the recombinant nucleic acid is a vector (e.g., an expression vector, a display vector, etc.). In some embodiments, the vector is a DNA vector or an RNA vector. Generally, vectors suitable for maintaining, propagating, and / or expressing polynucleotides to produce one or more polypeptides in a subject can be used. Examples of suitable vectors may include, for example, plasmids, cosmids, episomes, transposons, and viral vectors (e.g., adenoviral vectors, adeno-associated viral vectors, vaccinia viral vectors, Sindbis viral vectors, measles vectors, herpes viral vectors, lentiviral vectors, retroviral vectors, etc.). In some embodiments, the vector is a herpes viral vector. In some embodiments, the vector is capable of autonomous replication in a host cell. In some embodiments, the vector is incapable of autonomous replication in a host cell. In some Petition 870260060403, dated 06 / 19 / 2026, pages 150 / 300 138 / 237 embodiments, the vector can integrate into a host DNA. In some embodiments, the vector cannot integrate into a host DNA (e.g., it is episomal). Methods of producing vectors containing one or more polynucleotides of interest are well known to those skilled in the art, including, for example, by chemical synthesis, or by artificial manipulation of isolated nucleic acid segments (e.g., by genetic engineering techniques).

[00338] In some embodiments, a recombinant nucleic acid of the present disclosure is an amplicon of herpes simplex virus (HSV). Herpes virus amplicons, including their structural features and methods for producing them, are generally known to those skilled in the art (see, for example, de Silva S. and Bowers W. “Herpes Virus Amplicon Vectors”. Viruses 2009, 1, 594-629). In some embodiments, the herpes simplex virus amplicon is an HSV-1 amplicon. In some embodiments, the herpes simplex virus amplicon is a hybrid HSV-1 amplicon. Examples of HSV-1 hybrid amplicons may include, but are not limited to, HSV / AAV hybrid amplicons, HSV / EBV hybrid amplicons, HSV / EBV / RV hybrid amplicons, and / or HSV / Sleeping Beauty hybrid amplicons. In some embodiments, the amplicon is an HSV / AAV hybrid amplicon. In some embodiments, the amplicon is an HSV / Sleeping Beauty hybrid amplicon.

[00339] In some embodiments, a recombinant nucleic acid of the present disclosure is a recombinant herpesvirus genome. The recombinant herpesvirus genome may be a recombinant genome of any member of the Herpesviridae family of DNA viruses known in the art, including, for example, 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 genome of Petition 870260060403, dated 06 / 19 / 2026, page 151 / 300 139 / 237 recombinant herpesvirus 7, a recombinant Kaposi's sarcoma-associated herpesvirus genome, and any combinations or derivatives thereof. In some embodiments, the recombinant herpesvirus genome comprises one or more (e.g., one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, etc.) inactivating mutations. In some embodiments, one or more inactivating mutations are in one or more (e.g., one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, etc.) herpesvirus genes. In some embodiments, the recombinant herpesvirus genome is attenuated (e.g., compared to a corresponding wild-type herpesvirus genome). In some embodiments, the recombinant herpesvirus genome is replication-competent.In some forms, the genome of the recombinant herpes virus is defective for replication.

[00340] In some embodiments, the recombinant nucleic acid is a recombinant herpes simplex virus (HSV) genome. In some embodiments, 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. In some embodiments, the recombinant herpes simplex virus genome is a recombinant HSV-1 genome. In some embodiments, the recombinant herpes simplex virus genome is replication-competent. In some embodiments, the recombinant herpes simplex virus genome is replication-defective. In some embodiments, the recombinant herpes simplex virus genome comprises one or more (e.g., one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, etc.) inactivating mutations.In some forms, one or more inactivating mutations are present in one or more (e.g., one or more, two or more, three or more). Petition 870260060403, dated 06 / 19 / 2026, page 152 / 300 140 / 237 four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, etc.) genes of the herpes simplex virus. As used in this document, an inactivating mutation may refer to any mutation that results in a gene or regulon product (RNA or protein) having reduced quantity and / or function, being undetectable or eliminated (e.g., compared to a corresponding sequence without the inactivating mutation). Examples of inactivating mutations may include, but are not limited to, deletions, insertions, point mutations, and rearrangements in transcription control sequences (promoters, enhancers, insulators, etc.) and / or coding sequences of a given gene or regulon. Any method suitable for measuring the quantity of a gene or regulon product known in the art may be used, including, for example, qPCR, Northern blots, RNAseq, Western blots, ELISAs, etc.

[00341] In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in at least one, at least two, at least three, at least four, at least five, at least six, at least seven, or all eight of the infected cellular protein (or infected cellular polypeptide) (ICP) 0, ICP4, ICP22, ICP27, ICP47, thymidine kinase (tk), Long Unique Region (UL) 41, and / or UL55 genes of the herpes simplex virus. In some embodiments, the recombinant herpes simplex virus genome does not comprise an inactivating mutation in the herpes simplex virus genes ICP34.5 and / or ICP47 (e.g., to prevent the production of an immune-stimulating virus). In some embodiments, the recombinant herpes simplex virus genome does not comprise an inactivating mutation in the herpes simplex virus gene ICP34.5 (one or both copies).In some embodiments, the genome of the recombinant herpes simplex virus does not comprise an inactivating mutation in the herpes simplex virus gene ICP47. In some embodiments, the genome of the recombinant herpes simplex virus does not comprise an inactivating mutation in the virus genes. Petition 870260060403, dated 06 / 19 / 2026, page 153 / 300 141 / 237 herpes simplex ICP34.5 (one or both copies) and ICP47. In some embodiments, the recombinant herpes simplex virus genome is not oncolytic.

[00342] In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP0 gene (one or both copies). In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP0 gene (one or both copies) and further comprises an initiation mutation in the ICP4 (one or both copies) ICP22, ICP27, ICP47, UL41 and / or UL55 genes. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP0 gene (one or both copies) and an inactivation mutation in the ICP4 gene (one or both copies). In some forms, the genome of the recombinant herpes simplex virus comprises an inactivating mutation in the ICP0 gene (one or both copies), and an inactivating mutation in the ICP22 gene.In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP0 gene (one or both copies) and an inactivation mutation in the UL41 gene. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP0 gene (one or both copies), an inactivation mutation in the ICP4 gene (one or both copies), and an inactivation mutation in the ICP22 gene. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP0 gene (one or both copies), an inactivation mutation in the ICP4 gene (one or both copies), and an inactivation mutation in the UL41 gene. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP0 gene (one or both copies), an inactivation mutation in the ICP22 gene, and an inactivation mutation in the UL41 gene.In some forms, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP0 gene (one or both copies). Petition 870260060403, dated 06 / 19 / 2026, p. 154 / 300 142 / 237 inactivation mutation in the ICP4 gene (one or both copies), an inactivation mutation in the ICP22 gene, and an inactivation mutation in the UL41 gene. In some embodiments, the inactivation mutation is a deletion of the coding sequence of the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, and / or UL41 genes. In some embodiments, the recombinant herpes simplex virus genome further comprises an inactivation mutation in the ICP27, ICP47, and / or UL55 genes.

[00343] In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP4 gene (one or both copies). In some embodiments, the recombinant herpes complex virus genome comprises an inactivation mutation in the ICP4 gene (one or both copies) and further comprises an inactivation mutation in the ICP0 gene (one or both copies), ICP22, ICP27, ICP47, UL41 and / or UL55 genes. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP4 gene (one or both copies), and an inactivation mutation in the ICP22 gene. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP4 gene (one or both copies) and an inactivation mutation in the UL41 gene.In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP4 gene (one or both copies), an inactivating mutation in the ICP22 gene, and an inactivating mutation in the UL41 gene. In some embodiments, the inactivating mutation is a deletion of the coding sequence of the ICP4 (one or both copies), ICP22, and / or UL41 genes. In some embodiments, the recombinant herpes simplex virus genome further comprises an inactivating mutation in the ICP0, ICP27, ICP47, and / or UL55 genes.

[00344] In some embodiments, the genome of the recombinant herpes simplex virus comprises an inactivating mutation in the ICP22 gene. In some embodiments, the genome of the recombinant herpes simplex virus Petition 870260060403, dated 06 / 19 / 2026, pp. 155 / 300 143 / 237 comprises an inactivating mutation in the ICP22 gene and further comprises an inactivating mutation in the ICP0 (one or both copies), ICP4 (one or both copies), ICP27, ICP47, UL41, and / or UL55 genes. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP22 gene and an inactivating mutation in the UL41 gene. In some embodiments, the inactivating mutation is a deletion of the coding sequence of the ICP22 and / or UL41 genes. In some embodiments, the recombinant herpes simplex virus genome further comprises an inactivating mutation in the ICP0 (one or both copies), ICP4 (one or both copies), ICP27, ICP47, and / or UL55 genes.

[00345] In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP27 gene. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP27 gene and further comprises an inactivation mutation in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP47, UL41, and / or UL55 genes. In some embodiments, the inactivation mutation is a deletion of the coding sequence of the ICP27 gene.

[00346] In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP47 gene. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the ICP47 gene and further comprises an inactivation mutation in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, UL41, and / or UL55 genes. In some embodiments, the inactivation mutation is a deletion of the coding sequence of the ICP47 gene.

[00347] In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the UL41 gene. In some embodiments, the recombinant herpes simplex virus genome Petition 870260060403, dated 06 / 19 / 2026, page 156 / 300 144 / 237 comprises an inactivating mutation in the UL41 gene and further comprises an inactivating mutation in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, ICP47, and / or UL55 genes. In some embodiments, the inactivating mutation is a deletion of the coding sequence of the UL41 gene.

[00348] In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the UL55 gene. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivation mutation in the UL55 gene and further comprises an inactivation mutation in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, ICP47, and / or UL41 genes. In some embodiments, the inactivation mutation is a deletion of the coding sequence of the UL55 gene.

[00349] In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation (e.g., a deletion) of the internal repeat (joint) region comprising the long internal repeat (IRL) and short internal repeat (IRS) regions. In some embodiments, inactivation (e.g., deletion) of the joint region eliminates one copy of each of the ICP4 and ICP0 genes. In some embodiments, inactivation (e.g., deletion) of the joint region further inactivates (e.g., deletes) the promoter for the ICP22 and ICP47 genes. If desired, the expression of one or both genes can be restored by inserting an immediate early promoter into the genome of the recombinant herpes simplex virus (see, for example, Hill et al. (1995). Nature 375(6530): 411-415; Goldsmith et al. (1998). J Exp Med 187(3): 341-348).Without wishing to be limited by theory, it is believed that inactivation (e.g., deletion) of the junction region may contribute to the stability of the recombinant herpes simplex virus genome and / or allow the recombinant herpes simplex virus genome to accommodate more transgenes and / or larger transgenes. Petition 870260060403, dated 06 / 19 / 2026, page 157 / 300 145 / 237

[00350] In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP4 (one or both copies), ICP22, and ICP27 genes. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP4 (one or both copies), ICP27, and UL55 genes. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP4 (one or both copies), ICP22, ICP27, ICP47, and UL55 genes. In some embodiments, the inactivating mutation in the ICP4 (one or both copies), ICP27, and / or UL55 genes is a deletion of the coding sequence of the ICP4 (one or both copies), ICP27, and / or UL55 genes. In some forms, the inactivating mutation in the ICP22 and ICP47 genes is a deletion in the promoter region of the ICP22 and ICP47 genes (for example, the ICP22 and ICP47 coding sequences are intact but not transcriptionally active).In some embodiments, the recombinant herpes simplex virus genome comprises a deletion in the coding sequence of the ICP4 (one or both copies), ICP27, and UL55 genes, and a deletion in the promoter region of the ICP22 and ICP47 genes. In some embodiments, the recombinant herpes simplex virus genome also comprises an inactivating mutation in the ICP0 and / or UL41 genes.

[00351] In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP0 gene (one or both copies). In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP0 (one or both copies) and ICP4 (one or both copies) genes. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP0 (one or both copies), ICP4 (one or both copies), and ICP22 genes. In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, and ICP27 genes. In some Petition 870260060403, dated 06 / 19 / 2026, pp. 158 / 300 In some embodiments, the recombinant herpes simplex virus genome comprises an inactivating mutation in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, and UL55 genes. In some embodiments, the inactivating mutation in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, and / or UL55 genes comprises a deletion of the coding sequence of the ICP0, ICP4 (one or both copies), ICP22, ICP27, and / or UL55 genes. In some embodiments, the recombinant herpes simplex virus genome further comprises an inactivating mutation in the ICP47 and / or UL41 genes.

[00352] In some embodiments, a recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure at one, two, three, four, five, six, seven, or more viral gene loci. Examples of suitable viral loci may include, without limitation, loci of the viral herpes simplex gene ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, ICP47, tk, UL41, and UL55. In some embodiments, a recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure within one or both loci of the viral ICP4 gene (e.g., a recombinant virus carrying a first polynucleotide encoding a first human collagen protein at one or both ICP4 loci; a recombinant virus carrying a second polynucleotide encoding a second human collagen protein at one or both ICP4 loci; etc.).In some embodiments, a recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure within the viral ICP22 gene locus (e.g., a recombinant virus carrying a first polynucleotide encoding a first human collagen protein at the ICP22 locus; a recombinant virus carrying a second polynucleotide encoding a second human collagen protein at the ICP22 locus; etc.). In some embodiments, a herpes simplex virus genome... Petition 870260060403, dated 06 / 19 / 2026, page 159 / 300 147 / 237 recombinant simplex comprises one or more polynucleotides of the present disclosure within the viral UL41 gene locus (e.g., a recombinant virus carrying a first polynucleotide encoding a first human collagen protein at the UL41 locus; a recombinant virus carrying a second polynucleotide encoding a second human collagen protein at the UL41 locus; etc.).In some embodiments, a recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure at one or both loci of the viral ICP4 gene and one or more polynucleotides of the present disclosure within the viral ICP22 locus (for example, a recombinant virus carrying a first polynucleotide encoding a first human collagen protein at one or both ICP4 loci and a second polynucleotide encoding a second human collagen protein at the ICP22 locus; a recombinant virus carrying a second polynucleotide encoding a second human collagen protein at one or both ICP4 loci and a first polynucleotide encoding a first human collagen protein at the ICP22 locus; etc.).In some embodiments, a recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure at one or both loci of the viral ICP4 gene and one or more polynucleotides of the present disclosure within the viral UL41 locus (for example, a recombinant virus carrying a first polynucleotide encoding a first human collagen protein at one or both ICP4 loci and a second polynucleotide encoding a second human collagen protein at the UL41 locus; a recombinant virus carrying a second polynucleotide encoding a second human collagen protein at one or both ICP4 loci and a first polynucleotide encoding a first human collagen protein at the UL41 locus; etc.). In some embodiments, a recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure at one or both loci. Petition 870260060403, dated 06 / 19 / 2026, pp. 160 / 300 148 / 237 both loci of the viral ICP4 gene and one or more polynucleotides of the present disclosure within the viral ICP22 locus, and one or more polynucleotides of the present disclosure within the viral UL41 locus (for example, a recombinant virus carrying a first polynucleotide encoding a first human collagen protein at one or both ICP4 loci and a second polynucleotide encoding a second human collagen protein at the ICP22 and UL41 loci; a recombinant virus carrying a second polynucleotide encoding a second human collagen protein at one or both ICP4 loci and a first polynucleotide encoding a first human collagen protein at the ICP22 and UL41 loci; etc.).

[00353] In some embodiments, the recombinant herpesvirus genome (e.g., a recombinant herpes simplex virus genome) has been engineered to decrease or eliminate the expression of one or more toxic herpes simplex genes (such as one or both copies of the HSV ICP0 gene, one or both copies of the HSV ICP4 gene, the ICP22 gene, and / or the UL41 gene). In some embodiments, the recombinant herpesvirus genome (e.g., a recombinant herpes simplex virus genome) has been engineered to reduce the cytotoxicity of the recombinant genome (e.g., when introduced into a target cell) compared to a corresponding wild-type herpesvirus genome (e.g., a wild-type herpes simplex virus genome).In some embodiments, the cytotoxicity (e.g., in human keratinocytes and / or fibroblast cells) of the recombinant virus genome (e.g., a recombinant herpes simplex virus genome) is reduced by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%. Petition 870260060403, dated 06 / 19 / 2026, p. 161 / 300 149 / 237 at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% compared to a corresponding wild-type herpes simplex virus genome (e.g., measuring the relative cytotoxicity of a recombinant ΔICP4 herpes simplex virus genome (one or both copies) vs. a wild-type herpes simplex virus genome in human keratinocytes or fibroblasts (primary cells or cell lines); measuring the relative cytotoxicity of a recombinant ΔICP4 herpes simplex virus genome (one or both copies) / ΔICP22 versus a wild-type herpes simplex virus genome in human keratinocytes or fibroblasts (primary cells or cell lines); etc.). In some modalities, the cytotoxicity (e.g., in human keratinocytes and / or fibroblast cells) of the recombinant herpes virus genome (e.g.,a recombinant herpes simplex virus genome) is reduced by at least about 1.5 times, at least about 2 times, at least about 3 times, at least about 4 times, at least about 5 times, at least about 6 times, at least about 7 times, at least about 8 times, at least about 9 times, at least about 10 times, at least about 15 times, at least about 20 times, at least about 25 times, at least about 50 times, at least about 75 times, at least about 100 times, at least about 250 times, at least about 500 times, at least about 750 times, at least about 1000 times, or more compared to a corresponding wild-type herpes virus genome (e.g.,To measure the relative cytotoxicity of a recombinant ΔICP4 herpes simplex virus genome (one or both copies) versus a wild-type herpes simplex virus genome in human keratinocytes or fibroblasts (primary cells or cell lines); to measure the relative cytotoxicity of a recombinant ΔICP4 herpes simplex virus genome (one or both copies) / ΔICP22 versus a wild-type herpes simplex virus genome. Petition 870260060403, dated 06 / 19 / 2026, page 162 / 300 150 / 237 of wild-type herpes simplex virus in human keratinocytes or fibroblasts (primary cells or cell lines); etc.). Methods for measuring cytotoxicity are known to those skilled in the art, including, for example, through the use of vital dyes (formazan dyes), protease biomarkers, an MTT assay (or an assay using related tetrazolium salts such as XTT, MTS, water-soluble tetrazolium salts, etc.), measurement of ATP content, etc.

[00354] In some embodiments, the recombinant herpesvirus genome (e.g., a recombinant herpes simplex virus genome) has been engineered to reduce its impact on host cell proliferation after exposure of the target cell to the recombinant genome, compared to a corresponding wild-type herpesvirus genome (e.g., a wild-type herpes simplex virus genome). In some embodiments, the target cell is a human cell. In some embodiments, the target cell is an epidermal and / or dermal cell. In some embodiments, the target cell is a keratinocyte and / or fibroblast.In some embodiments, the proliferation of host cells (e.g., human keratinocytes and / or fibroblast cells) after exposure to the recombinant genome is at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% faster compared with the proliferation of host cells after exposure to a corresponding wild-type herpesvirus genome. (for example, measuring relative cell proliferation after exposure to a recombinant ΔIOP4 herpes simplex virus genome (one or more). Petition 870260060403, dated 06 / 19 / 2026, p. 163 / 300 151 / 237 both copies) versus cell proliferation after exposure to a wild-type herpes simplex virus genome in human keratinocytes or fibroblasts (primary cells or cell lines); measuring relative cell proliferation after exposure to a recombinant ΔICP4 herpes simplex virus genome (one or both copies) / ΔICP22 versus cell proliferation after exposure to a wild-type herpes simplex virus genome in human keratinocytes or fibroblasts (primary cells or cell lines); etc.). In some embodiments, the proliferation of host cells (e.g., human keratinocytes and / or fibroblast cells) after exposure to the recombinant genome is at least about 1.5-fold, at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold,at least about 10 times, at least about 15 times, at least about 20 times, at least about 25 times, at least about 50 times, at least about 75 times, at least about 100 times, at least about 250 times, at least about 500 times, at least about 750 times, or at least about 1000 times faster compared with the proliferation of the host cell after exposure to a corresponding wild-type herpesvirus genome (e.g.,Measuring relative cell proliferation after exposure to a recombinant ΔICP4 herpes simplex virus genome (one or both copies) versus cell proliferation after exposure to a wild-type herpes simplex virus genome in human keratinocytes or fibroblasts (primary cells or cell lines); measuring relative cell proliferation after exposure to a recombinant ΔICP4 herpes simplex virus genome (one or both copies) / ΔICP22 versus cell proliferation after exposure to a wild-type herpes simplex virus genome in human keratinocytes or fibroblasts (primary cells or cell lines); etc.). The methods for measuring cell proliferation are, Petition 870260060403, dated 06 / 19 / 2026, page 164 / 300 152 / 237 known to those skilled in the art, including, for example, through the use of a Ki67 cell proliferation assay, a BrdU cell proliferation assay, etc.

[00355] A vector (e.g., herpes viral vector) may include one or more polynucleotides of the present disclosure in a form suitable for expression of the polynucleotide in a host cell. Vectors may include one or more regulatory sequences operationally linked to the polynucleotide to be expressed (e.g., as described above).

[00356] In some embodiments, a recombinant nucleic acid of the present disclosure (e.g., a recombinant herpes simplex virus genome) comprises one or more of the polynucleotides described herein inserted in any orientation in the recombinant nucleic acid. If the recombinant nucleic acid comprises two or more polynucleotides described herein (e.g., two or more, three or more, etc.), the polynucleotides may be inserted in the same orientation or in orientations opposite to each other. Without wishing to be limited by theory, incorporating two polynucleotides (e.g., two transgenes) into a recombinant nucleic acid (e.g., a vector) in an antisense orientation may help to avoid misreading and ensure proper expression of each polynucleotide. Virus

[00357] Certain aspects of the present disclosure relate to viruses comprising any of the recombinant polynucleotides and / or nucleic acids described herein. In some embodiments, the virus is capable of infecting one or more target cells of a subject (e.g., a human). In some embodiments, the virus is suitable for delivering the recombinant polynucleotides and / or nucleic acids into one or more target cells of a subject (e.g., a human subject). In some embodiments, one or more target cells are one or more human cells. In some embodiments, one or more target cells are one or more cells of Petition 870260060403, dated 06 / 19 / 2026, pp. 165 / 300 153 / 237 skin (e.g., one or more cells from the epidermis, dermis, and / or subcutaneous tissue). In some embodiments, one or more cells are selected from keratinocytes, melanocytes, Langerhans cells, Merkel cells, mast cells, fibroblasts, and / or adipocytes. In some embodiments, one or more cells are keratinocytes. In some embodiments, one or more cells reside in the stratum corneum, stratum granulosum, stratum spinosum, stratum basale, and / or basement membrane. In some embodiments, one or more target cells are one or more epidermal cells.

[00358] Any suitable virus known in the art may be used, including, for example, adenovirus, adeno-associated virus, retrovirus, lentivirus, sendai virus, herpes virus (e.g., a herpes simplex virus), vaccinia virus and / or any hybrid virus thereof. In some embodiments, the virus is attenuated. In some embodiments, the virus is defective in replication. In some aspects, the virus is competent for replication. In some embodiments, the virus has been modified to alter its tissue tropism relative to the tissue tropism of an unmodified wild-type virus. In some embodiments, the virus has reduced cytotoxicity compared with a corresponding wild-type virus. The methods for producing a virus comprising recombinant nucleic acids are well known to those skilled in the art.

[00359] In some embodiments, the virus is a member of the Herpesviridae family of DNA viruses, including, for example, a herpes simplex virus, a varicella-zoster virus, a human cytomegalovirus, a herpesvirus 6A, a herpesvirus 6B, a herpesvirus 7, and a herpesvirus associated with Kaposi's sarcoma, etc. In some embodiments, the herpes virus is attenuated. In some embodiments, the herpes virus is defective in replication. In some aspects, the herpes virus is competent for replication. In some embodiments, the herpes virus has reduced cytotoxicity compared to a corresponding wild-type herpes virus. In some embodiments, the Petition 870260060403, dated 06 / 19 / 2026, page 166 / 300 154 / 237 herpes virus is not oncolytic.

[00360] In some embodiments, the virus is a herpes simplex virus. Herpes simplex viruses comprising recombinant nucleic acids may be produced by a disclosed process, for example, in WO2015 / 009952 and / or WO2017 / 176336. In some embodiments, the herpes simplex virus is attenuated. In some embodiments, the herpes simplex virus is replication-competent. In some embodiments, the herpes simplex virus is replication-defective. 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). In some embodiments, the HSV-1 is attenuated. In some embodiments, the HSV-1 has reduced cytotoxicity compared to a corresponding wild-type HSV-1. In some modalities, HSV-1 is not oncolytic.

[00361] In some embodiments, the herpes simplex virus has been modified to alter its tissue tropism relative to the tissue tropism of an unmodified wild-type herpes simplex virus. In some embodiments, the herpes simplex virus comprises a modified envelope. In some embodiments, the modified envelope comprises one or more (e.g., one or more, two or more, three or more, four or more, etc.) mutant herpes simplex virus glycoproteins. Examples of herpes simplex virus glycoproteins may include, but are not limited to, gB, gC, gD, gH, and gL glycoproteins. In some embodiments, the modified envelope alters the tissue tropism of the herpes simplex virus relative to a wild-type herpes simplex virus.

[00362] In some embodiments, the transduction efficiency (in vitro and / or in vivo) of a virus of the present disclosure (e.g., a herpes virus) to one or more target cells (e.g., one or more human keratinocytes and / or fibroblasts) is at least about 25%. For example, the efficiency Petition 870260060403, dated 06 / 19 / 2026, p. 167 / 300 155 / 237 The transduction efficiency of the virus to one or more target cells may be at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 99%, at least about 99.5% or more. In some embodiments, the virus is a herpes simplex virus and the transduction efficiency of the virus to one or more target cells (e.g., one or more human keratinocytes and / or fibroblasts) is about 85% to about 100%.In some embodiments, the virus is a herpes simplex virus and the transduction efficiency of the virus to one or more target cells (e.g., one or more human keratinocytes and / or fibroblasts) is at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or 100%. Methods for measuring viral transduction efficiency in vitro or in vivo are well known to those skilled in the art, including, for example, qPCR analysis, deep sequencing, western blotting, fluorometric analysis (such as fluorescence in situ hybridization (FISH), fluorescent reporter gene expression, immunofluorescence, FACS), etc. Compositions and Formulations.

[00363] Certain aspects of this disclosure relate to compositions and formulations (for example, pharmaceutical compositions and formulations) comprising any of the recombinant nucleic acids (for example, a recombinant herpes virus genome) and / or viruses (for example, a herpes virus comprising a recombinant genome described herein (such as a herpes simplex virus comprising a genome)). Petition 870260060403, dated 06 / 19 / 2026, page 168 / 300 156 / 237 recombinant herpes simplex virus) and an excipient or carrier (e.g., a pharmaceutically acceptable excipient or carrier). In some embodiments, the composition or formulation is a cosmetic composition or formulation (e.g., a skin care product).

[00364] In some embodiments, the composition or formulation comprises any one or more of the viruses (e.g., herpes virus) described herein. In some embodiments, the composition or formulation comprises from about 10⁴ to about 10¹² plaque-forming units (PFU) / mL of the virus. For example, the composition or formulation may comprise about 104a about 1012, about 105a about 1012, about 106a about 1012, about 107a about 1012, about 108 to about 1012, about 109 to about 1012, about 1010a about 1012, about 1011a about 1012, about 104a about 1011, about 105a about 1011, about 106a about 1011, about 107a about 1011, about 108 to about 1011, about 109 to about 1011, about 1010a about 1011, about 104a about 1010, about 105 to about 1010, about 106 to about 1010, about 107 to about 1010, about 108 to about 1010, about 109 to about 1010, about 104 to about 109,approximately 105 to approximately 109, approximately 106 to approximately 109, approximately 107 to approximately 109, approximately 108 to approximately 109, approximately 104 to approximately 108, approximately 105 to approximately 108, approximately 106 to approximately 108, approximately 107 to approximately 108, approximately 104 to approximately 107, approximately 105 to approximately 107, approximately 106 to approximately 107, approximately 104 to approximately 106, approximately 105 to approximately 106, or approximately 104 to approximately 105 PFU / mL of the virus. In some embodiments, the composition or formulation comprises approximately 104, approximately 105, approximately 106, approximately 107, approximately 108, approximately 109, approximately 1010, approximately 1011, or approximately 1012 PFU / mL of the virus.

[00365] The compositions and formulations (e.g., pharmaceutical compositions and formulations), as described in this document, may be prepared by mixing the active ingredient(s) (such as a recombinant nucleic acid or a virus) with the desired degree of purity with one or more Petition 870260060403, dated 06 / 19 / 2026, pp. 169 / 300 157 / 237 Acceptable carriers or excipients. Pharmaceutically acceptable carriers (e.g., pharmaceutically acceptable carriers or excipients) are generally non-toxic to recipients at the dosages and concentrations used and may include, but are not limited to: buffers (such as phosphate, citrate, acetate and other organic acids); antioxidants (such as ascorbic acid and methionine); preservatives (such as octadecyldimethylbenzyl ammonium chloride, benzalkonium chloride, benzethonium chloride, phenol, butyl or benzyl alcohol, alkyl parabens, catechol, resorcinol, cyclohexanol, 3-pentanol and m-cresol); amino acids (such as glycine, glutamine, asparagine, histidine, arginine or lysine); low molecular weight polypeptides (less than about 10 residues); proteins (such as serum albumin, gelatin or immunoglobulins); Polyols (such as glycerol, for example, formulations including 10% glycerol);Hydrophilic polymers (such as polyvinylpyrrolidone); monosaccharides, disaccharides, and other carbohydrates (including glucose, mannose, or dextrins); chelating agents (such as EDTA); sugars (such as sucrose, mannitol, trehalose, or sorbitol); salt-forming counter-ions (such as sodium); metal complexes (such as Zn-protein complexes); liposomes (e.g., cationic lipids); nanoparticle carriers; and / or nonionic surfactants (such as polyethylene glycol (PEG)). A complete discussion of carriers is available in REMINGTON'S PHARMACEUTICAL SCIENCES (Mack Pub. Co., NJ 1991).

[00366] In some embodiments, the composition or formulation comprises one or more lipid carriers (e.g., cationic lipid). In some embodiments, the composition or formulation comprises one or more nanoparticle carriers. Nanoparticles are submicron-sized (less than about 1000 nm) drug delivery vehicles that can carry encapsulated drugs (such as small synthetic molecules, proteins, peptides, cells, viruses, and biotherapeutics) Petition 870260060403, dated 06 / 19 / 2026, pp. 170 / 300 158 / 237 nucleic acid base for rapid or controlled release. A variety of molecules (e.g., proteins, peptides, recombinant nucleic acids, etc.) can be efficiently encapsulated in nanoparticles using processes well known in the art. In some embodiments, a molecule encapsulated in a nanoparticle may refer to a molecule (such as a virus) that is contained within the nanoparticle or bound to and / or associated with the surface of the nanoparticle, or any combination thereof. Nanoparticles for use in the compositions or formulations described herein may be any type of biocompatible nanoparticle known in the art, including, for example, nanoparticles comprising poly(lactic acid), poly(glycolic acid), PLGA, PLA, PGA and any combinations thereof (see, for example, Vauthier et al. Adv Drug Del Rev. (2003) 55: 519-48; US2007 / 0148074; US2007 / 0092575; US2006 / 0246139; US5753234; US7081483; and WO2006 / 052285).

[00367] In some embodiments, the carrier or excipient (e.g., a pharmaceutically acceptable carrier or excipient) may be adapted for or suitable for any route of administration known in the art, including, for example, intravenous, intramuscular, subcutaneous, cutaneous, intranasal, intratracheal, sublingual, buccal, topical, oral, transdermal, intradermal, intraperitoneal, intraorbital, intravitreal, subretinal, transmucosal, intra-articular, by surface injection, by implantation, by inhalation, intrathecal, intraventricular and / or intranasal administration. In some embodiments, the carrier or excipient (e.g., a pharmaceutically acceptable carrier or excipient) is adapted or suitable for topical, transdermal, subcutaneous and / or intradermal administration. In some embodiments, the carrier or excipient is adapted or suitable for topical, transdermal and / or intradermal administration.In some embodiments, the carrier or excipient is adapted or suitable for surface injection.

[00368] Examples of adapted carriers or excipients or Petition 870260060403, dated 06 / 19 / 2026, p. 171 / 300 159 / 237 Suitable for use in topical, transdermal, subcutaneous, superficial and / or intradermal application / administration may include, but are not limited to, ointments, oils, pastes, creams, aerosols, suspensions, emulsions, greasy ointments, gels, powders, liquids, lotions, solutions, sprays, patches (e.g., transdermal patches or microneedle patches), adhesive strips, a microneedle or microneedle arrangements, and inhalants. In some embodiments, the carrier or excipient (e.g., the pharmaceutically acceptable carrier or excipient) comprises one or more (e.g., one or more, two or more, three or more, four or more, five or more, etc.) of an ointment, oil, paste, cream, aerosol, suspension, emulsion, greasy ointment, gel, powder, liquid lotion, solution, spray, adhesive strip, and an inhalant.In some embodiments, the carrier comprises an adhesive (e.g., a patch that adheres to the skin), such as a transdermal patch or a microneedle patch. In some embodiments, the carrier comprises a microneedle or microneedle array. Methods for making and using microneedle arrays suitable for composition delivery are generally known in the art (Kim Y. et al. “Microneedles for drug and vaccine delivery”. Advanced Drug Delivery Reviews 2012, 64 (14): 1547-68).

[00369] In some embodiments, the composition or formulation (e.g., the pharmaceutical composition or formulation) is adapted or suitable for any route of administration known in the art, including, for example, intravenous, intramuscular, subcutaneous, cutaneous, oral, intranasal, intratracheal, sublingual, buccal, topical, transdermal, intradermal, intraperitoneal, intraorbital, intravitreal, subretinal, transmucosal, intraarticular, by surface injection, by implantation, inhalation, intrathecal, intraventricular and / or intranasal administration. In some embodiments, the composition or formulation is adapted for or suitable for cutaneous, topical, transdermal, subcutaneous and / or intradermal administration. In some embodiments, the pharmaceutical composition or formulation is adapted or suitable for Petition 870260060403, dated 06 / 19 / 2026, p. 172 / 300 160 / 237 Topical, transdermal and / or intradermal administration. In some embodiments, the composition or formulation is adapted or suitable for intradermal administration. In some embodiments, the composition of the formulation is adapted or suitable for superficial injection.

[00370] In some embodiments, the composition or formulation (e.g., pharmaceutical composition or formulation) further comprises one or more additional components. Examples of additional components may include, but are not limited to, binding agents (e.g., pregelatinized corn starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose, etc.); fillers (e.g., lactose and other sugars, microcrystalline cellulose, pectin, gelatin, calcium sulfate, ethyl cellulose, polyacrylates or calcium hydrogen phosphate, etc.); lubricants (e.g., magnesium stearate, talc, silica, colloidal silicon dioxide, stearic acid, metallic stearates, hydrogenated vegetable oils, corn starch, polyethylene glycols, sodium benzoate, sodium acetate, etc.); disintegrants (e.g., starch, sodium starch glycolate, etc.); humectants (e.g., sodium lauryl sulfate, etc.); saline solutions; alcohols; polyethylene glycols; gelatin; lactose; amylase; magnesium stearate; talc; silicic acid; viscous paraffin; hydroxymethylcellulose; polyvinylpyrrolidone; sweeteners; flavorings; perfumes; colorants; moisturizers; sunscreens; antibacterial agents; agents capable of stabilizing polynucleotides or preventing their degradation and the like. In some embodiments, the composition or formulation comprises a hydroxypropylmethylcellulose gel. In some embodiments, the composition or formulation comprises a phosphate buffer. In some embodiments, the composition or formulation comprises glycerol (for example, in about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 15%, etc.).

[00371] The compositions and formulations (e.g., pharmaceutical compositions and formulations) to be used for in vivo administration are. Petition 870260060403, dated 06 / 19 / 2026, page 173 / 300 161 / 237 generally sterile. Sterility can be easily achieved, for example, by filtration through sterile filtration membranes.

[00372] In some embodiments, any of the recombinant nucleic acids, viruses, and / or compositions or formulations described herein may be used to deliver one or more polynucleotides encoding a collagen protein (e.g., a human collagen protein such as Collagen 3) into one or more cells of a subject (e.g., one or more collagen-deficient cells). In some embodiments, any of the recombinant nucleic acids, viruses, and / or compositions or formulations described herein may be used in a therapy. In some embodiments, any of the recombinant nucleic acids, viruses, and / or compositions or formulations described herein may be used in the treatment of a cosmetic or aesthetic condition that would benefit from the expression of a collagen polypeptide (e.g., a cosmetic or aesthetic condition associated with a collagen deficiency (such as aged and / or UV-damaged skin)).In some embodiments, any of the recombinant nucleic acids, viruses, and / or compositions or formulations described herein may be used in the treatment of dermatological aging (for example, as described below).

[00373] In some embodiments, any of the recombinant nucleic acids, viruses, and / or compositions or formulations described herein may be used in the preparation or manufacture of a medicament. In s...

Claims

1. Use of a cosmetic composition, characterized in that it is in the manufacture of a medicament to reduce one or more signs or symptoms of dermatological aging, comprising: a herpes simplex virus comprising a recombinant herpes simplex virus genome, wherein the recombinant herpes simplex virus genome comprises a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein, wherein the first collagen protein is selected from the group consisting of an alpha-1(I) collagen polypeptide (COL1-1), an alpha-2(I) collagen polypeptide (COL1-2), an alpha-1(II) collagen polypeptide (COL2), an alpha-1(III) collagen polypeptide (COL3), an alpha-1(IV) collagen polypeptide (COL41), an alpha-2(IV) collagen polypeptide (COL4-2), an alpha-3(IV) collagen polypeptide (COL4-3), and an alpha-4(IV) collagen polypeptide. (COL4-4),an alpha-5(IV) collagen polypeptide (COL4-5), an alpha-6(IV) collagen polypeptide (COL4-6), an alpha-1(V) collagen polypeptide (COL5-1), an alpha-2(V) collagen polypeptide (COL5-2), an alpha-3(V) collagen polypeptide (COL5-3), an alpha-1(VI) collagen polypeptide (COL6-1), an alpha-2(VI) collagen polypeptide (COL6-2), an alpha-3(VI) collagen polypeptide (COL6-3), an alpha-4(VI) collagen polypeptide (COL6-4), an alpha-5(VI) collagen polypeptide (COL6-5), an alpha-6(VI) collagen polypeptide (COL6-6), an alpha-1(VIII) collagen polypeptide (COL8), an alpha-1(IX) collagen polypeptide (COL9-1), an alpha-2 chain polypeptide (IX) of collagen (COL9-2), an alpha-3 chain polypeptide (IX) of collagen (COL9-3), an alpha-1 chain polypeptide (X) of collagen (COL10),an alpha-1(XI) chain polypeptide of collagen Petition 870260060403, dated 06 / 19 / 2026, page. 251 / 300 2 / 6 (COL11-1), an alpha-2(XI) collagen chain polypeptide (COL11-2), an alpha-1(XII) collagen chain polypeptide (COL12), an alpha-1(XIII) collagen chain polypeptide (COL13), an alpha-1(XIV) collagen chain polypeptide (COL14), an alpha-1(XV) collagen chain polypeptide (COL15), an alpha-1(XVI) collagen chain polypeptide (COL16), an alpha-1(XVII) collagen chain polypeptide (COL17), an alpha-1(XVIII) collagen chain polypeptide (COL18), an alpha-1(XIX) collagen chain polypeptide (COL19), an alpha-1(XX) collagen chain polypeptide (COL20), an alpha-1(XXI) collagen chain polypeptide (COL21), an alpha-1(XXII) collagen chain polypeptide collagen (COL22), an alpha-1(XXIII) chain polypeptide of collagen (COL23), an alpha-1(XXIV) chain polypeptide of collagen (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), 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 and a first fibrillin protein, and wherein the recombinant herpes simplex virus genome does not comprise a polynucleotide encoding a collagen alpha-1(VII) chain polypeptide, a lysyl hydroxylase 3 polypeptide or a type I keratin cytoskeleton polypeptide 17., 2. Use according to claim 1, characterized in that the reduction of one or more dermatological signs of aging is indicated by: (a) treatment, reduction and / or prevention of fine lines and / or wrinkles; (b) reduction in skin pore size; (c) improvement in skin thickness, smoothness and / or firmness; (d) improvement in the smoothness, elasticity and / or softness of the skin. Petition 870260060403, dated 06 / 19 / 2026, page 1.252 / 300 3 / 6 skin; (e) improvement in skin tone, brightness and / or clarity; (f) improvement in procollagen and / or collagen production; (g) improvement in skin texture and / or promotion of retexturization; (h) improvement in the appearance of skin contours; (i) restoration of skin brightness and / or clarity; (j) improvement in the appearance of skin diminished by aging and / or menopause; (k) improvement in skin hydration; (l) increase in skin elasticity and / or resilience; (m) treatment, reduction and / or prevention of skin sagging; (n) improvement in skin firmness; (o) reduction of pigment spots, skin blemishes and / or scars); (p) improvement of the optical properties of the skin by light diffraction or reflection; or (q) any combination thereof.

3. Use of a cosmetic composition, characterized by the fact that it is in the manufacture of a medicament to improve the condition, quality and / or appearance of the skin, comprising: a herpes simplex virus comprising a recombinant herpes simplex virus genome, wherein the recombinant herpes simplex virus genome comprises a first polynucleotide encoding a first polypeptide comprising a first cosmetic protein, wherein the first collagen protein is selected from the group consisting of an alpha-1(I) collagen polypeptide (COL1-1), an alpha-2(I) collagen polypeptide (COL1-2), an alpha-1(II) collagen polypeptide (COL2), an alpha-1(III) collagen polypeptide (COL3), an alpha-1(IV) collagen polypeptide (COL41), an alpha-2(IV) collagen polypeptide (COL4-2), an alpha-3(IV) collagen polypeptide (COL4-3), and an alpha-4(IV) collagen polypeptide. (COL4-4),an alpha-5(IV) chain polypeptide of collagen (COL4-5), an alpha-6(IV) chain polypeptide of collagen (COL4-6), an alpha-1(V) chain polypeptide of collagen (COL5-1), an alpha-2(V) chain polypeptide of collagen (COL5-2), an alpha-3(V) chain polypeptide of collagen (COL5-3), an alpha-1(VI) chain polypeptide Petition 870260060403, dated 06 / 19 / 2026, page. 253 / 300 4 / 6 of collagen (COL6-1), an alpha-2(VI) chain polypeptide of collagen (COL6-2), an alpha-3(VI) chain polypeptide of collagen (COL6-3), an alpha-4(VI) chain polypeptide of collagen (COL6-4), an alpha-5(VI) chain polypeptide of collagen (COL6-5), an alpha-6(VI) chain polypeptide of collagen (COL6-6), an alpha-1(VIII) chain polypeptide of collagen (COL8), an alpha-1(IX) chain polypeptide of collagen (COL9-1), an alpha-2(IX) chain polypeptide of collagen (COL9-2), an alpha-3(IX) chain polypeptide of collagen (COL9-3), an alpha-1(X) chain polypeptide of collagen (COL10),an alpha-1(XI) collagen chain polypeptide (COL11-1), an alpha-2(XI) collagen chain polypeptide (COL11-2), an alpha-1(XII) collagen chain polypeptide (COL12), an alpha-1(XIII) collagen chain polypeptide (COL13), an alpha-1(XIV) collagen chain polypeptide (COL14), an alpha-1(XV) collagen chain polypeptide (COL15), an alpha-1(XVI) collagen chain polypeptide (COL16), an alpha-1(XVII) collagen chain polypeptide (COL17), an alpha-1(XVIII) collagen chain polypeptide (COL18), an alpha-1(XIX) collagen chain polypeptide (COL19), an alpha-1(XX) collagen chain polypeptide (COL20), an alpha-1(XXI) collagen chain polypeptide (COL21), an alpha-1(XXII) chain polypeptide of collagen (COL22), an alpha-1(XXIII) chain polypeptide of collagen (COL23), an alpha-1(XXIV) chain polypeptide of collagen (COL24), an alpha-1(XXV) chain polypeptide of collagen (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), 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 and a first fibrillin protein, and Petition 870260060403, dated 06 / 19 / 2026, p. 254 / 300 5 / 6 whereby the recombinant herpes simplex virus genome does not comprise a polynucleotide encoding a collagen alpha-1 (VII) chain polypeptide, a lysyl hydroxylase 3 polypeptide or a type I keratin cytoskeleton polypeptide 17., 4. Use in accordance with any one of claims 1 to 3, characterized in that the genome of the recombinant herpes simplex virus is a genome of recombinant herpes simplex virus type 1 (HSV-1).

5. Use in accordance with any one of claims 1 to 4, characterized in that the genome of the recombinant herpes simplex virus comprises an inactivating mutation in one or both copies of the ICP4 gene.

6. Use in accordance with any one of claims 1 to 5, characterized in that the first polynucleotide encoding the first polypeptide is at one or both loci of the viral gene ICP4.

7. Use in accordance with any one of claims 1 to 6, characterized in that the first cosmetic protein comprises a sequence with at least 95% to 100% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 15, SEQ ID NO: 17, and SEQ ID NOS: 53-64.

8. Use in accordance with any one of claims 1 to 7, characterized in that the genome of the recombinant herpes simplex virus further comprises a second polynucleotide encoding a second polypeptide comprising a second cosmetic protein.

9. Use according to claim 8, characterized in that the first and second cosmetic proteins are different.

10. Use according to claim 8, characterized in that the first and second cosmetic proteins are identical.

11. Use according to any of claims 1 to 10, characterized in that the herpes virus is defective for replication. Petition 870260060403, dated 06 / 19 / 2026, pp. 255 / 300 6 / 6 12. Use in accordance with any of claims 1 to 11, characterized in that the cosmetic composition is suitable for topical, transdermal, subcutaneous, intradermal, oral, intranasal, intratracheal, sublingual, buccal, rectal, vaginal, urethral, ​​inhaled, intravenous, intra-arterial, intramuscular, intracardiac, intraosseous, intraperitoneal, transmucosal, intravitreal, subretinal, intra-articular, peri-articular, local or epicutaneous administration.

13. Use in accordance with any of claims 1 to 12, characterized in that the cosmetic composition is suitable for intradermal administration.

14. Use in accordance with any of claims 1 to 13, characterized in that the cosmetic composition is suitable for superficial injection.

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