CA2326407A1 - Retroviral vectors including modified envelope escort proteins - Google Patents

Retroviral vectors including modified envelope escort proteins Download PDF

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Publication number
CA2326407A1
CA2326407A1 CA002326407A CA2326407A CA2326407A1 CA 2326407 A1 CA2326407 A1 CA 2326407A1 CA 002326407 A CA002326407 A CA 002326407A CA 2326407 A CA2326407 A CA 2326407A CA 2326407 A1 CA2326407 A1 CA 2326407A1
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protein
retroviral
modified
vector
envelope protein
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CA2326407C (en
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Frederick L. Hall
Erlinda Maria Gordon
W. French Anderson
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University of Southern California USC
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    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/13011—Gammaretrovirus, e.g. murine leukeamia virus
    • C12N2740/13041—Use of virus, viral particle or viral elements as a vector
    • C12N2740/13043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/13011—Gammaretrovirus, e.g. murine leukeamia virus
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    • C12N2740/13045—Special targeting system for viral vectors
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    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/40—Vectors comprising a peptide as targeting moiety, e.g. a synthetic peptide, from undefined source
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    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/40—Vectors comprising a peptide as targeting moiety, e.g. a synthetic peptide, from undefined source
    • C12N2810/405—Vectors comprising RGD peptide
    • C—CHEMISTRY; METALLURGY
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    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
    • C12N2810/55—Vectors comprising as targeting moiety peptide derived from defined protein from bacteria
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    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
    • C12N2810/80—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates
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    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
    • C12N2810/80—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates
    • C12N2810/85—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates mammalian
    • C12N2810/851—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates mammalian from growth factors; from growth regulators
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    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
    • C12N2810/80—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates
    • C12N2810/85—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates mammalian
    • C12N2810/857—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates mammalian from blood coagulation or fibrinolysis factors
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    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
    • C12N2810/80—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates
    • C12N2810/85—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates mammalian
    • C12N2810/859—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates mammalian from immunoglobulins

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Abstract

A retroviral vector comprising a first retroviral envelope protein and at least one modified retroviral envelope protein, wherein said first retroviral envelope protein includes a surface protein comprising (i) a receptor binding region; (ii) a hypervariable polyproline region; and (iii) a body portion, and said modified retroviral envelope protein, prior to modification, includes a surface protein which includes (i) a receptor binding region; (ii) a hypervariable polyproline region; and (iii) a body portion, characterized in that said modified retroviral envelope protein has been modified such that at least 90 % of the amino acid residues of the receptor binding region of said surface protein of said modified retroviral envelope protein have been removed and replaced with a non-retroviral protein or peptide.

Claims (22)

1. A retroviral vector comprising a first retroviral envelope protein and at least one modified retroviral envelope protein, wherein said first retroviral envelope protein includes a surface protein comprising (i) a receptor binding region; (ii) a hypervariable polyproline region; and (iii) a body portion, and said modified retroviral envelope protein, prior to modification, includes a surface protein which includes (i) a receptor binding region; (ii) a hypervariable polyproline region; and (iii) a body portion, characterized in that said modified retroviral envelope protein has been modified such that at least 90% of the amino acid residues of the receptor binding region of said surface protein of said modified retroviral envelope protein have been removed and replaced with a non-retroviral protein or peptide.
2. The vector of Claim 1 wherein at least 92% of the amino acid residues of the receptor binding region of said surface protein of said modified retroviral envelope protein have been removed and replaced with a non-retroviral protein or peptide.
3. The vector of Claim 2 wherein all of the amino acid residues of the receptor binding region of said surface protein of said modified retroviral envelope protein have been removed and replaced with a non-retroviral protein or peptide.
4. The vector of Claim 1 wherein at least 90% of the amino acid residues of the receptor binding region of said surface protein of said modified retroviral envelope protein and at least a portion of the amino acid residues of said hypervariable polyproline region of said surface protein of said modified retroviral envelope protein have been removed and replaced with a non-retroviral protein or peptide.
5. The vector of Claim 1 wherein, prior to modification thereof, said receptor binding region of said modified retroviral envelope protein has the sequence (SEQ ID
NO:1), and wherein, in said modified retroviral envelope protein, amino acid residues through 229 of (SEQ ID NO:1) have been removed and replaced with a non-retroviral protein or peptide.
6. The vector of Claim 5 wherein amino acid residues 19 through 229 of (SEQ ID
NO:1), and at least a portion of the amino acid residues of said hypervariable polyproline region of said surface protein of said modified retroviral envelope protein have been removed and replaced with said non-retroviral protein or peptide.
7. The vector of Claim 6 wherein said hypervariable polyproline region of said surface protein of said modified retroviral envelope protein has the sequence (SEQ ID
NO:
2), and amino acid residues 19 through 229 of (SEQ ID NO:1) and amino acid residues 1 through 35 of (SEQ ID NO:2) have been removed and replaced with said non-retroviral protein or peptide.
8. The vector of Claim 7 wherein said hypervariable polyproline region of said surface protein of said modified retroviral envelope protein has the sequence (SEQ ID
NO:2), and amino acid residues 19 through 229 of (SEQ ID NO:1) and amino acid residues 1 through 48 of (SEQ ID NO:2) have been removed and replaced with said non-retroviral protein or peptide.
9. The vector of Claim 8 wherein said hypervariable polyproline region of said surface protein of said modified retroviral envelope protein has the sequence (SEQ ID
NO:2), and amino acid residues 19 through 229 of (SEQ ID NO:1) and amino acid residues 1 through 60 of (SEQ ID NO:2) have been removed and replaced with said non-retroviral protein or peptide.
10. The vector of Claim 1 wherein said vector includes said first retroviral envelope protein and a modified retroviral envelope protein, wherein, prior to modification, said modified retroviral envelope protein includes a surface protein which includes (i) a receptor binding region; (ii) a hypervariable polyproline region; and (iii) a body portion, wherein said modified retroviral envelope protein has been modified such that at least 90% of the amino acid residues of the receptor binding region of said surface protein of said modified retroviral envelope protein are removed and replaced with a ligand which binds to a desired target molecule.
11. The vector as claimed in claim 10 wherein said target molecule is an extracellular matrix component.
12. The vector of Claim 11 wherein said extracellular matrix component is collagen.
13. The vector as claimed in any one of claims 1 to 9 wherein said non-retroviral protein or peptide is a complement regulatory protein.
14. The vector of as claimed in any one of claims 1 to 9 wherein said non-retroviral protein or peptide is selected from the group consisting of Protein A, Protein ZZ, and VEGF.
15. The vector as claimed in any one of claims 1 to 9 wherein said vector includes a first modified retroviral envelope protein and a second modified retroviral envelope protein, wherein, in said first modified retroviral envelope protein, said non-retroviral protein or peptide is a ligand which binds to a desired target molecule, and in said second modified retroviral envelope protein, said non-retroviral protein or polypeptide is a complement regulatory protein.
16. The vector as claimed in any one of claims 1 to 15 wherein said vector further includes a polynucleotide encoding a polypeptide heterologous to said retrovirus.
17. The vector as claimed in any one of claims 1 to 15 wherein said first retroviral envelope protein is a wild-type retroviral envelope protein.
18. A modified polynucleotide encoding a modified retroviral envelope protein wherein prior to modification the envelope protein includes a surface protein including (i) a receptor binding region; (ii) a hypervariable polyproline region; and (iii) a body portion, and in the modified polynucleotide, a polynucleotide sequence encoding at least 90% of the amino acid residues of the receptor binding region of the surface protein is removed and replaced with a polynucleotide sequence encoding a non-retroviral protein or peptide.
19. A method of expressing a heterologous polypeptide in a host comprising:
administering to said host the vector as claimed in any one of Claims 1 to 17.
20. A method of expressing a heterologous polypeptide in a cell, comprising:

administering to said cell the vector as claimed in any one of Claims 1 to 17.
21. A modified retroviral envelope protein, wherein prior to modification, said modified retroviral envelope protein includes a surface protein comprising (i) a receptor binding region having the sequence (SEQ ID NO:1),; (ii) a hypervariable polyproline region having the sequence (SEQ ID NO: 2); and (iii) a body portion, wherein said modified retroviral envelope protein has been modified such that at least 90%
of the amino acid residues of the receptor binding region of said surface protein of said modified retroviral envelope protein have been removed and replaced with a non-retroviral protein or peptide characterized in that amino acid residues 1 through 35 of (SEQ ID NO:2) have been removed and replaced with said non-retroviral protein or peptide.
22. The protein of Claim 21 wherein, in said modified retroviral envelope protein, amino acid residues 19 through 229 of (SEQ ID NO:1) have been removed and replaced with a non-retroviral protein or peptide
CA2326407A 1998-04-29 1999-04-28 Retroviral vectors including modified envelope escort proteins Expired - Lifetime CA2326407C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US6939898A 1998-04-29 1998-04-29
US09/069,398 1998-04-29
PCT/IB1999/000764 WO1999055893A1 (en) 1998-04-29 1999-04-28 Retroviral vectors including modified envelope escort proteins

Publications (2)

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CA2326407A1 true CA2326407A1 (en) 1999-11-04
CA2326407C CA2326407C (en) 2012-09-11

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ID=22088734

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CA2326407A Expired - Lifetime CA2326407C (en) 1998-04-29 1999-04-28 Retroviral vectors including modified envelope escort proteins

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Country Link
EP (1) EP1073758A1 (en)
JP (1) JP2002514388A (en)
CA (1) CA2326407C (en)
IL (1) IL139016A0 (en)
NZ (2) NZ507645A (en)
WO (1) WO1999055893A1 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7078483B2 (en) 1998-04-29 2006-07-18 University Of Southern California Retroviral vectors including modified envelope escort proteins
WO2003087329A2 (en) * 2002-04-11 2003-10-23 University Of Southern California Targeted cytocidal virionoids for antiangiogenesis
WO2006007539A1 (en) * 2004-07-01 2006-01-19 Virxsys Corporation Vector packaging cell line
EP3155004B1 (en) * 2014-06-12 2021-01-13 Universidade do Porto - Reitoria Vaccine for immunocompromised hosts
MX2020007390A (en) * 2018-01-11 2020-10-14 Chameleon Biosciences Inc Immuno-evasive vectors and use for gene therapy.

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993014188A1 (en) * 1992-01-17 1993-07-22 The Regents Of The University Of Michigan Targeted virus
JPH10501403A (en) * 1994-03-04 1998-02-10 ユニバーシティ オブ メディシン アンド デンティストリー オブ ニュージャージー Cell-type-specific gene transfer using retroviral vectors containing antibody-envelope fusion proteins and wild-type envelope fusion proteins
US5643770A (en) * 1994-07-21 1997-07-01 Alexion Pharmaceuticals, Inc. Retroviral vector particles expressing complement inhibitor activity
EP0870040A2 (en) * 1995-12-29 1998-10-14 Chiron Corporation Gene delivery vehicle-targeting ligands

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IL139016A0 (en) 2001-11-25
NZ507645A (en) 2004-06-25
JP2002514388A (en) 2002-05-21
EP1073758A1 (en) 2001-02-07
WO1999055893A1 (en) 1999-11-04
NZ532894A (en) 2005-10-28
CA2326407C (en) 2012-09-11

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