EP1003896A1 - Vecteur de baculovirus modifie par coque de proteine s'utilisant en genotherapie - Google Patents

Vecteur de baculovirus modifie par coque de proteine s'utilisant en genotherapie

Info

Publication number
EP1003896A1
EP1003896A1 EP98947386A EP98947386A EP1003896A1 EP 1003896 A1 EP1003896 A1 EP 1003896A1 EP 98947386 A EP98947386 A EP 98947386A EP 98947386 A EP98947386 A EP 98947386A EP 1003896 A1 EP1003896 A1 EP 1003896A1
Authority
EP
European Patent Office
Prior art keywords
vector
vector according
virus
sequence
baculovirus
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.)
Withdrawn
Application number
EP98947386A
Other languages
German (de)
English (en)
Inventor
Christian Hofmann
Michael Strauss
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.)
Develogen AG
Original Assignee
HepaVec AG fur Gentherapie
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 HepaVec AG fur Gentherapie filed Critical HepaVec AG fur Gentherapie
Publication of EP1003896A1 publication Critical patent/EP1003896A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
    • 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
    • C12N2710/14011—Baculoviridae
    • C12N2710/14111—Nucleopolyhedrovirus, e.g. autographa californica nucleopolyhedrovirus
    • C12N2710/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2710/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

Definitions

  • the invention relates to a coat protein-modified baculovirus vector for gene therapy; Areas of application are medicine, biotechnology and genetic engineering.
  • baculovirus vector that can transfer therapeutic genes highly specifically and effectively into liver cells.
  • Baculoviruses belong to a family of large DNA viruses, the host spectrum of which is naturally restricted to arthropods. Your genome (80kbp-200kpb) is packaged in flexible nucleocapsids that allow the insertion of large amounts of foreign DNA.
  • the decisive prerequisite for bacuioviral gene transfer in mammalian cells is the insertion of an expression cassette that is functional in mammalian cells. This created an important prerequisite for the therapy of genetic diseases of the liver.
  • the aim of this invention is the construction of a Baculoviru ⁇ vector which, by modifying the virus envelope, escapes inactivation by serum components and transfers therapeutic genes highly specifically and effectively in liver cells in vivo.
  • the therapeutic DNA sequence for the vector according to the invention is the cDNA of a gene which is defective in the disease to be treated, i.e. missing or changed by mutation. It is also possible to use part of a genomic sequence which spans a mutation in the target gene and can homologously recombine with it.
  • the first line serves as strong viral promoters, preferably the very early promoter of the Cyto arcadeieviru ⁇ (CMV). Cell-specific protorotors are also suitable.
  • the establishment sequence has the task of stabilizing the vector in the cell without integration into the genome. It is used particularly in cases where long-term expression is required.
  • Preferred establishment sequences according to the invention are viral core establishment sequences, such as the Ep ⁇ tein-Barr virus, or autonomous replication sequences from the mammalian genome.
  • the new vectors are produced in the following essential steps:
  • a novel vector for gene transfer is created which offers considerable advantages over the virus vectors developed so far (retroviruses, adenoviruses and unmodified baculoviruses). These include the stability in blood and serum, the liver specificity or free variation of the cell targeting, the almost unlimited possibility of incorporating foreign DNA, the infection of cells that are unable to divide, the lack of cytotoxicity and the simple generation of high-titre recombinant viruses.
  • the envelope protein-modified Baculoviru ⁇ vectors enable a desired gene to be introduced into the affected organ of a patient and to optimally design his way to the functional site.
  • the application of the vector can be local or systematic. A essential prerequisite for successful therapy of genetic and malignant diseases of humans is thereby created. The invention will be explained in more detail below by means of exemplary embodiments.
  • Insect cells manufactured. 10 ul of the viruses were with 90 ul
  • a sequence for an N-terminally modified baculovirus envelope protein (gp64) is cloned in a known manner in a recombination vector under the control of a baculoviral promoter.
  • the modification is achieved by inserting the DNA sequence for amino acids 1-320 of the complement protection protein "decay accelerating factor (DAF)" between the signal sequence and the sequence of the baculovirus protein gp64 at the DNA level.
  • DAF decay accelerating factor
  • This construct is either cloned into the recombination vector, which contains the therapeutic DNA sequences together with the promoter, or is stably integrated into the virus packaging cell.
  • the modified coat protein is inserted into the envelope of the baculovirus vector and thereby mediates:

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Virology (AREA)
  • Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Toxicology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • Plant Pathology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne un vecteur de baculovirus modifié par coque de protéine s'utilisant en génothérapie et s'appliquant à la médecine, la biotechnologie et la technique génique. L'invention vise à la construction d'un vecteur de baculovirus présentant une stabilité élevée dans le sang, par modification de l'enveloppe virale et permettant de transférer et d'établir des gènes thérapeutiques, indépendamment de leur taille, dans des cellules mamméliennes, de manière hautement spécifique et efficace. Le vecteur doit pouvoir s'utiliser en génothérapie chez l'homme. Le vecteur obtenu selon l'invention comprend un virus d'insecte, de préférence un représentant des baculovirus ou d'un virus de la polyhédrose nucléaire, contenant les constituants suivants: des coques de protéines de virus modifiées, une séquence d'ADN thérapeutique, un promoteur adapté à l'expression génique et éventuellement une séquence d'établissement.
EP98947386A 1997-08-15 1998-08-05 Vecteur de baculovirus modifie par coque de proteine s'utilisant en genotherapie Withdrawn EP1003896A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE1997135593 DE19735593C2 (de) 1997-08-15 1997-08-15 Hüllprotein-modifizierter Baculovirus-Vektor für die Gentherapie
DE19735593 1997-08-15
PCT/DE1998/002255 WO1999009193A1 (fr) 1997-08-15 1998-08-05 Vecteur de baculovirus modifie par coque de proteine s'utilisant en genotherapie

Publications (1)

Publication Number Publication Date
EP1003896A1 true EP1003896A1 (fr) 2000-05-31

Family

ID=7839201

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98947386A Withdrawn EP1003896A1 (fr) 1997-08-15 1998-08-05 Vecteur de baculovirus modifie par coque de proteine s'utilisant en genotherapie

Country Status (6)

Country Link
EP (1) EP1003896A1 (fr)
JP (1) JP2003530064A (fr)
CA (1) CA2300362A1 (fr)
DE (1) DE19735593C2 (fr)
ES (1) ES2150894T1 (fr)
WO (1) WO1999009193A1 (fr)

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US6183993B1 (en) * 1996-09-11 2001-02-06 The General Hospital Corporation Complement-resistant non-mammalian DNA viruses and uses thereof
GB0012997D0 (en) * 2000-05-26 2000-07-19 Eurogene Limited Gene delivery
WO2002014527A2 (fr) * 2000-08-11 2002-02-21 Boyce Thompson Institute For Plant Research, Inc. Baculovirus nuls gp64, pseudotypes a l'aide de proteines d'enveloppe heterologues
CA2440342A1 (fr) 2001-03-12 2002-09-19 Ark Therapeutics Ltd. Vecteurs viraux pseudotypes par l'avidine et leur utilisation
WO2002096469A2 (fr) * 2001-05-29 2002-12-05 Ark Therapeutics Ltd. Transfert genique de vecteur viral
GB0119852D0 (en) 2001-08-15 2001-10-10 Univ York Baculovirus
US6863884B2 (en) 2002-05-01 2005-03-08 Cell Genesys, Inc. Pseudotyped retroviral vectors
EP1548119A4 (fr) * 2002-09-25 2006-08-02 Osaka Ind Promotion Org Vecteur de baculovirus, son procede de construction et procede de transfert genique
US7416890B2 (en) 2002-09-25 2008-08-26 Osaka Industrial Promotion Organization Baculovirus vector, method of producing thereof and method of gene transfer
US8906676B2 (en) 2004-02-02 2014-12-09 Ambrx, Inc. Modified human four helical bundle polypeptides and their uses
KR101699142B1 (ko) 2004-06-18 2017-01-23 암브룩스, 인코포레이티드 신규 항원-결합 폴리펩티드 및 이의 용도
GB0425739D0 (en) * 2004-11-23 2004-12-22 Procure Therapeutics Ltd Humanised baculovirus 2
SG158148A1 (en) 2004-12-22 2010-01-29 Ambrx Inc Compositions containing, methods involving, and uses of non-natural amino acids and polypeptides
CN103520735B (zh) 2004-12-22 2015-11-25 Ambrx公司 包含非天然编码的氨基酸的人生长激素配方
JP2008525473A (ja) 2004-12-22 2008-07-17 アンブレツクス・インコーポレイテツド 修飾されたヒト成長ホルモン
CA2590429C (fr) 2004-12-22 2014-10-07 Ambrx, Inc. Compositions de synthetase d'aminoacyl-arnt et utilisations correspondantes
MX2007007591A (es) 2004-12-22 2007-07-25 Ambrx Inc Metodos para expresion y purificacion de hormona de crecimiento humano recombinante.
JP2008541769A (ja) 2005-06-03 2008-11-27 アンブレツクス・インコーポレイテツド 改善されたヒトインターフェロン分子及びそれらの使用
PT2339014E (pt) 2005-11-16 2015-10-13 Ambrx Inc Métodos e composições compreendendo aminoácidos não-naturais
TWI477602B (zh) 2006-02-09 2015-03-21 Educational Foundation Jichi Medical Univ Novel viral vector
US9333249B2 (en) 2006-02-09 2016-05-10 Educational Foundation Jichi Medical University Recombinant baculovirus vaccine
KR20090060294A (ko) 2006-09-08 2009-06-11 암브룩스, 인코포레이티드 변형된 인간 혈장 폴리펩티드 또는 Ｆｃ 스캐폴드 및 그의 용도
WO2008030613A2 (fr) 2006-09-08 2008-03-13 Ambrx, Inc. Arnt suppresseur hybride pour cellules de vertébrés
CN104163864B (zh) 2007-03-30 2017-08-01 Ambrx公司 经修饰fgf‑21多肽和其用途
AU2008247815B2 (en) 2007-05-02 2012-09-06 Ambrx, Inc. Modified interferon beta polypeptides and their uses
JP5547083B2 (ja) 2007-11-20 2014-07-09 アンブルックス，インコーポレイテッド 修飾されたインスリンポリペプチドおよびそれらの使用
CN103694337B (zh) 2008-02-08 2016-03-02 Ambrx公司 经修饰瘦素多肽和其用途
UA118536C2 (uk) 2008-07-23 2019-02-11 Амбркс, Інк. Модифікований поліпептид бичачого гранулоцитарного колонієстимулювального фактора та його застосування
NZ607477A (en) 2008-09-26 2014-09-26 Ambrx Inc Non-natural amino acid replication-dependent microorganisms and vaccines
KR101647164B1 (ko) 2008-09-26 2016-08-09 암브룩스, 인코포레이티드 변형된 동물 에리트로포이에틴 폴리펩티드 및 이의 용도
CN107056929A (zh) 2009-12-21 2017-08-18 Ambrx 公司 经过修饰的猪促生长素多肽和其用途
CN107674121A (zh) 2009-12-21 2018-02-09 Ambrx 公司 经过修饰的牛促生长素多肽和其用途
US9567386B2 (en) 2010-08-17 2017-02-14 Ambrx, Inc. Therapeutic uses of modified relaxin polypeptides
MX346786B (es) 2010-08-17 2017-03-31 Ambrx Inc Polipeptidos de relaxina modificados y sus usos.
AR083006A1 (es) 2010-09-23 2013-01-23 Lilly Co Eli Formulaciones para el factor estimulante de colonias de granulocitos (g-csf) bovino y variantes de las mismas
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Also Published As

Publication number Publication date
ES2150894T1 (es) 2000-12-16
DE19735593C2 (de) 1999-08-26
CA2300362A1 (fr) 1999-02-25
DE19735593A1 (de) 1999-02-18
WO1999009193A1 (fr) 1999-02-25
JP2003530064A (ja) 2003-10-14

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