CA2318492A1 - Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells - Google Patents

Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells Download PDF

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Publication number
CA2318492A1
CA2318492A1 CA002318492A CA2318492A CA2318492A1 CA 2318492 A1 CA2318492 A1 CA 2318492A1 CA 002318492 A CA002318492 A CA 002318492A CA 2318492 A CA2318492 A CA 2318492A CA 2318492 A1 CA2318492 A1 CA 2318492A1
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CA
Canada
Prior art keywords
adenovirus
vehicle according
anyone
capsid
tissue tropism
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002318492A
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French (fr)
Other versions
CA2318492C (en
Inventor
Menzo Jans Emco Havenga
Abraham Bout
Ronald Vogels
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Janssen Vaccines and Prevention BV
Original Assignee
Introgene B.V.
Menzo Jans Emco Havenga
Abraham Bout
Ronald Vogels
Crucell Holland B.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Introgene B.V., Menzo Jans Emco Havenga, Abraham Bout, Ronald Vogels, Crucell Holland B.V. filed Critical Introgene B.V.
Publication of CA2318492A1 publication Critical patent/CA2318492A1/en
Application granted granted Critical
Publication of CA2318492C publication Critical patent/CA2318492C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10341—Use of virus, viral particle or viral elements as a vector
    • C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10341—Use of virus, viral particle or viral elements as a vector
    • C12N2710/10345—Special targeting system for viral vectors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
    • C12N2810/60—Vectors comprising as targeting moiety peptide derived from defined protein from viruses
    • C12N2810/6009—Vectors comprising as targeting moiety peptide derived from defined protein from viruses dsDNA viruses
    • C12N2810/6018—Adenoviridae

Abstract

The invention provides a nucleic acid delivery vehicle with or having been provided with at least a tissue tropism for smooth muscle cells and/or endothelial cells. In one aspect said nucleic acid delivery vehicle is a virus capsid or a functional part, derivative and/or analogue thereof. Preferably said virus capsid is an adnovirus capsid. Preferably said adenovirus is a subgroup B adenovirus, preferably adenovirus 16. Preferably said tissue tropism is provided by at least a tissue tropism determining part of an adenovirus fiber protein or a functional derivative and/or analogue thereof. The invention further presents methods for the treatment of diseases, preferably cardiovascular diseases.

Claims (37)

1. A gene delivery vehicle having been provided with at least a tissue tropism for smooth muscle cells and/or endothelial cells.
2. A gene delivery vehicle having been deprived of at least a tissue tropism for liver cells.
3. A vehicle according to claim 1 wherein said vehicle has been deprived of at least a tissue tropism for liver cells.
4. A vehicle according to anyone of the claims 1-3, wherein said tissue tropism is being provided by a virus capsid.
5. A vehicle according to claim 4, wherein said capsid comprises protein fragments from at least two different viruses.
6. A vehicle according to claim 5, wherein at least one of said viruses is an adenovirus.
7. A vehicle according to claim 5 or claim 6, wherein at least one of said viruses is an adenovirus of subgroup B.
8. A vehicle according to anyone of the claims 5-7, wherein at least one of said protein fragments comprises a tissue tropism determining fragment of a fiber protein derived from a subgroup B adenovirus.
9. A vehicle according to anyone of the claim 7 or claim 8, wherein said subgroup B adenovirus is adenovirus 16.
10. A vehicle according to claim 7-9, wherein protein fragments not derived from an adenovirus of subgroup B are derived from an adenovirus of subgroup C, preferably of adenovirus 5.
11. A vehicle according to anyone of the claims 1-10 comprising a nucleic acid derived from an adenovirus.
12. A vehicle according to anyone of the claims 1-11, comprising a nucleic acid derived from at least two different adenoviruses.
13. A vehicle according to claim 11 or claim 12, wherein said nucleic acid comprises at least one sequence encoding a fiber protein comprising at least a tissue tropism determining fragment of a subgroup B adenovirus fiber protein, preferably of adenovirus 16.
14. A vehicle according anyone of the claims 10-13, wherein said adenovirus nucleic acid is modified such that the capacity of said adenovirus nucleic acid to replicate in a target cell has been reduced or disabled.
15. A vehicle according to anyone of the claims 11-14, wherein said adenovirus nucleic acid is modified such that the capacity of a host immune system to mount an immune response against adenovirus proteins encoded by said adenovirus nucleic acid has been reduced or disabled.
16. A vehicle according to anyone of the claims 1-15, comprising a minimal adenovirus vector or an Ad/AAV chimaeric vector.
17. A vehicle according to anyone of the claims 1-16, further comprising at least one non-adenovirus nucleic acid.
18. A vehicle according to claim 17 wherein at least one of said non-adenovirus nucleic acids is a gene selected from the group of genes encoding: an apolipoprotein, a nitric oxide synthase, a herpes simplex virus thymidine kinase, an interleukin-3, an interleukin-l.alpha., an (anti)angiogenesis protein such as angiostatin, an anti-proliferation protein, a smooth muscle cell anti-migration protein, a vascular endothelial growth factor (VGEF), a basic fibroblast growth factor, a hypoxia inducible factor la (HIF-l.alpha.) or a PAI-1.
19. A cell for the production of a vector according to anyone of the claims 1-18, comprising means for the assembly of said vectors wherein said means includes a means for the production of an adenovirus fiber protein, wherein said fiber protein comprises at least a tissue tropism determining fragment of a subgroup B adenovirus fiber protein.
20. A cell according to claim 19, wherein said cell is or is derived from a PER. C6 cell (ECACC deposit number 96022940).
21. The use of a vehicle according to anyone of the claims 1-18 as a pharmaceutical.
22. The use of claim 21 for the treatment of cardiovascular disease.
23. The use of claim 21 for the treatment of a disease, treatable by transfer of a therapeutic nucleic acid to smooth muscle cells and/or endothelial cells.
24. An adenovirus capsid with or provided with a tissue tropism for smooth muscle cells and/or endothelial cells wherein said capsid preferably comprises proteins from at least two different adenoviruses and wherein at least a tissue tropism determining fragment of a fiber protein is derived from a subgroup B adenovirus, preferably of adenovirus 16.
25. An adenovirus capsid having been deprived of a tissue tropism for liver cells wherein said capsid preferably comprises proteins from at least two different adenoviruses and wherein at least a tissue tropism determining fragment of a fiber protein is derived from a subgroup B adenovirus, preferably of adenovirus 16.
26. The use of an adenovirus capsid according to claim 24 and/or claim 25, for the delivery of nucleic acid to smooth muscle cells and/or endothelial cells.
27. The use of an adenovirus capsid according to claim 26, in a medicament for the treatment of a disease.
28. Construct pBr/Ad.BamR.DELTA.Fib, comprising adenovirus 5 sequences 21562-31094 and 32794-35938.
29. Construct pBr/AdBamRfib16, comprising adenovirus 5 sequences 21562-31094 and 32794-35938, further comprising an adenovirus,l6 gene encoding fiber protein.
30. Construct pBr/AdBamR.pac/fib16, comprising adenovirus sequences 21562-31094 and 32794-35938, further comprising an adenovirus 16 gene encoding fiber protein, and further comprising a unique PacI-site in the proximity of the adenovirus 5 right terminal repeat, in the non-adenovirus sequence backbone of said construct.
31. Construct pWE/Ad.AfIIIrITRfib16, comprising adenovirus sequences 3534-31094 and 32794-35938, further comprising an adenovirus 16 gene encoding fiber protein.
32. Construct pWE/Ad.AfIIIrITRDE2Afib16, comprising adenovirus 5 sequences 3534-22443, 24033-31094 and 32794-35938, further comprising an adenovirus 16 gene encoding fiber protein.
33. The use of a construct according to anyone of the claims 28-32 for the generation of a vehicle according to anyone of the claims 1-18 or an adenovirus capsid according to claim 24 or claim 25.
34. The production of a vehicle according to anyone of the claims 1-18 or a adenovirus capsid according to claim 24 or claim 25.
35. The use of a vehicle according to anyone of the claims 1-18 for the generation a gene library.
36. The use of a fiber protein of adenovirus 16 for the delivery of nucleic acid to smooth muscle. cells and/or endothelial cells.
37. The use of a fiber protein of adenovirus 16 in an adenovirus capsid for depriving said capsid of a tissue tropism for liver cells.
CA2318492A 1998-11-20 1999-11-22 Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells Expired - Fee Related CA2318492C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP98203921 1998-11-20
EP98203921.6 1998-11-20
PCT/NL1999/000717 WO2000031285A1 (en) 1998-11-20 1999-11-22 Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells

Publications (2)

Publication Number Publication Date
CA2318492A1 true CA2318492A1 (en) 2000-06-02
CA2318492C CA2318492C (en) 2010-05-11

Family

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Family Applications (1)

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CA2318492A Expired - Fee Related CA2318492C (en) 1998-11-20 1999-11-22 Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells

Country Status (12)

Country Link
JP (1) JP4683682B2 (en)
AT (1) ATE296894T1 (en)
AU (1) AU770780B2 (en)
CA (1) CA2318492C (en)
DE (1) DE69925567T2 (en)
ES (1) ES2244145T3 (en)
IL (1) IL133032A (en)
MX (1) MXPA99010682A (en)
NO (1) NO995697L (en)
NZ (1) NZ501214A (en)
WO (1) WO2000031285A1 (en)
ZA (1) ZA997213B (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6929946B1 (en) 1998-11-20 2005-08-16 Crucell Holland B.V. Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells
WO2000052186A1 (en) * 1999-03-04 2000-09-08 Introgene B.V. Means and methods for fibroblast-like or macrophage-like cell transduction
US6492169B1 (en) 1999-05-18 2002-12-10 Crucell Holland, B.V. Complementing cell lines
EP1285079A2 (en) 2000-05-31 2003-02-26 University of Saskatchewan Modified bovine adenovirus having altered tropism
EP1322774A2 (en) * 2000-09-20 2003-07-02 Crucell Holland B.V. Gene delivery vectors provided with a tissue tropism for dendritic cells
US6905678B2 (en) * 2001-07-07 2005-06-14 Crucell Holland B.V. Gene delivery vectors with cell type specificity for mesenchymal stem cells
EP1482052A1 (en) * 2003-05-27 2004-12-01 Cytos Biotechnology AG Modified polypeptides for targeting cell-entry of the adenoviruses of subtype B
WO2018218240A1 (en) 2017-05-26 2018-11-29 Epicentrx, Inc. Recombinant adenoviruses carrying transgenes

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5770442A (en) * 1995-02-21 1998-06-23 Cornell Research Foundation, Inc. Chimeric adenoviral fiber protein and methods of using same
SI0833934T2 (en) * 1995-06-15 2013-04-30 Crucell Holland B.V. Packaging systems for human recombinant adenovirus to be used in gene therapy
CA2236912C (en) * 1995-11-28 2006-04-25 Genvec, Inc. Vectors and methods for gene transfer to cells
US5877011A (en) * 1996-11-20 1999-03-02 Genzyme Corporation Chimeric adenoviral vectors
FR2758822B1 (en) * 1997-01-30 1999-07-02 Centre Nat Rech Scient USE OF A POLYPEPTIDE AS A CELLULAR RECEPTOR OF ADENOVIRUS
FR2761689B1 (en) * 1997-04-02 1999-06-25 Transgene Sa MODIFIED ADENOVIRAL FIBER AND TARGET ADENOVIRUS

Also Published As

Publication number Publication date
ZA997213B (en) 2000-05-22
AU5960099A (en) 2000-05-25
CA2318492C (en) 2010-05-11
DE69925567D1 (en) 2005-07-07
AU770780B2 (en) 2004-03-04
ES2244145T3 (en) 2005-12-01
ATE296894T1 (en) 2005-06-15
WO2000031285A1 (en) 2000-06-02
IL133032A (en) 2007-06-03
NZ501214A (en) 2002-02-01
JP4683682B2 (en) 2011-05-18
JP2000157289A (en) 2000-06-13
DE69925567T2 (en) 2006-05-04
MXPA99010682A (en) 2002-03-08
IL133032A0 (en) 2001-03-19
NO995697L (en) 2000-05-22
NO995697D0 (en) 1999-11-19

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