# US 2019/0314525 A1 · Synthetic adenoviruses targeting bone tissue and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0314525 A1 - Document ID: US20190314525A1 - Status: Published application - Kind: A1 - Application number: 16/448,671 - Filed: 2019-06-21 - Published: 2019-10-17 - Earliest claimed: 2016-12-30 - Assignees: The Salk Institute for Biological Studies - Applicants: Salk Institute for Biological Studies - Inventors: Clodagh O'Shea; Colin Powers; Lei Zhang - Web page: https://patentgrep.com/patent/US20190314525A1 ## CPC - A61K 48/0041: {the non-active part being polymeric} - A61K 38/1875: {Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor} - A61K 38/29: Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides - A61K 38/30: Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 {(insulin-like growth factor binding protein A61K38/1754)} - A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct} - A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease - C07K 14/005: from viruses - C12N 9/0069: {acting on single donors with incorporation of molecular oxygen, i.e. oxygenases (1.13)} - C12N 9/1241: {Nucleotidyltransferases (2.7.7)} - C12N 15/86: Viral vectors - C12Y 113/12007: Photinus-luciferin 4-monooxygenase (ATP-hydrolysing) (1.13.12.7), i.e. firefly-luciferase - A61K 48/0008: {characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition} - A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered} - C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies - C12N 2710/10322: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2710/10345: Special targeting system for viral vectors - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - C12Y: ENZYMES ## Abstract Synthetic adenoviruses with tropism to bone tissue are described. The synthetic adenoviruses include an adenovirus type 11 (Ad11) fiber protein or a chimeric adenovirus fiber protein having an Ad11 knob domain. The synthetic adenoviruses can also include a transgene, such as a reporter gene or a transgene encoding a factor that promotes bone regeneration or repair. Use of the synthetic adenoviruses to target bone tissue and/or to promote bone repair or regeneration is also described. ## Claims ### Claim 1 A method of expressing a transgene in bone tissue of a subject, comprising administering to the subject a synthetic adenovirus comprising: the transgene; and a fiber protein from adenovirus serotype 11 (Ad11), or a chimeric fiber protein having an Ad11 knob domain. ### Claim 2 (depends on 1) The method of claim 1, wherein the transgene is a reporter gene. ### Claim 3 (depends on 2) The method of claim 2, wherein the reporter gene encodes a fluorescent protein or an enzyme. ### Claim 4 (depends on 1) The method of claim 1, wherein the transgene encodes a factor that promotes bone repair or regeneration. ### Claim 5 A method of promoting bone repair or regeneration in a subject, comprising administering to the subject a synthetic adenovirus comprising: a transgene encoding a factor that promotes bone repair or regeneration; and a fiber protein from adenovirus serotype 11 (Ad11), or a chimeric fiber protein having an Ad11 knob domain. ### Claim 6 (depends on 5) The method of claim 5, wherein the factor that promotes bone repair or regeneration is a bone morphogenetic protein (BMP), Wnt, insulin-like growth factor I (IGF-I), or parathyroid hormone. ### Claim 7 (depends on 6) The method of claim 6, wherein the BMP is BMP-2, BMP-4, BMP-6 or BMP-7. ### Claim 8 (depends on 5) The method of claim 5, wherein the synthetic adenovirus comprises two or more transgenes encoding a factor that promotes bone repair or regeneration. ### Claim 9 (depends on 8) The method of claim 8, wherein the synthetic virus comprises four transgenes encoding a BMP, Wnt, IGF-I and parathyroid hormone. ### Claim 10 (depends on 5) The method of claim 5, wherein the synthetic adenovirus further comprises a native or modified capsid that detargets the synthetic virus from the liver. ### Claim 11 (depends on 10) The method of claim 10, wherein the synthetic adenovirus comprises a modified hexon protein that detargets the virus from the liver. ### Claim 12 (depends on 5) The method of claim 5, wherein the synthetic adenovirus comprises Ad5 capsid proteins and a chimeric fiber protein comprising an Ad5 shaft domain and an Ad11 knob domain. ### Claim 13 (depends on 5) The method of claim 5, wherein expression of the factor that promotes bone repair or regeneration is regulated by a tissue-specific promoter. ### Claim 14 (depends on 13) The method of claim 13, wherein the tissue-specific promoter is active in bone tissue. ### Claim 15 (depends on 5) The method of claim 5, wherein the synthetic adenovirus further comprises one or more binding sites for a liver-specific microRNA and/or one or more binding sites for a spleen-specific microRNA. ### Claim 16 (depends on 15) The method of claim 15, wherein the liver-specific microRNA is miR-122 and/or the spleen-specific microRNA is miR142-3p. ### Claim 17 (depends on 15) The method of claim 15, wherein the one or more binding sites are in the 3′UTR of the transgene. ### Claim 18 (depends on 1) The method of claim 1, wherein the genome of the synthetic adenovirus comprises a nucleotide sequence at least 95% identical to SEQ ID NO: 2 or SEQ ID NO: 6, or comprises the nucleotide sequence of SEQ ID NO: 2 or SEQ ID NO: 6. ### Claim 19 A synthetic adenovirus genome, comprising a nucleotide sequence at least 95% identical to SEQ ID NO: 2 or SEQ ID NO: 6. ### Claim 20 (depends on 19) The synthetic adenovirus genome of claim 19, comprising SEQ ID NO: 2 or SEQ ID NO: 6.