WO1996029096A1 - Preparation de transfert genique - Google Patents
Preparation de transfert genique Download PDFInfo
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- WO1996029096A1 WO1996029096A1 PCT/JP1996/000652 JP9600652W WO9629096A1 WO 1996029096 A1 WO1996029096 A1 WO 1996029096A1 JP 9600652 W JP9600652 W JP 9600652W WO 9629096 A1 WO9629096 A1 WO 9629096A1
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- vector
- gene
- cells
- virus
- freeze
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- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 108090000623 proteins and genes Proteins 0.000 title abstract description 52
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 8
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- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims abstract description 7
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims abstract description 6
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- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims abstract description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 5
- 229930195725 Mannitol Natural products 0.000 claims abstract description 5
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims abstract description 5
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims abstract description 5
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- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims abstract description 4
- 239000004475 Arginine Substances 0.000 claims abstract description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims abstract description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims abstract description 4
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims abstract description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims abstract description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 4
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- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims abstract description 4
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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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- 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
- 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
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/13011—Gammaretrovirus, e.g. murine leukeamia virus
- C12N2740/13051—Methods of production or purification of viral material
Definitions
- the present invention relates to a method for producing a freeze-dried preparation of a virus vector for gene therapy which is safe and excellent in storage stability, and a gene-introduced preparation obtained by the method.
- Gene therapy is divided into germ cell gene therapy (germ line cell gene therapy) and somatic cell gene therapy (somatic cell gene therapy) depending on the type of cells (target cells) into which the gene is to be introduced. It has been. Addition gene therapy (Augmentation Gene Therapy) that adds a new (normal) gene while leaving the abnormal (cause) gene intact y) and Replacement gene therapy (Replacement gene therapy), which replaces abnormal genes with normal genes. At present, however, only additional gene therapy for somatic cells is considered due to ethical and technical constraints. Has been done.
- autologous transplantation is a method in which target cells are first removed from the patient, the target gene is introduced, and then the cells are returned to the patient's body (ex Vivo gene therapy).
- Retroviruses are enveloped RNA viruses that enter the cell by binding their envelope proteins to receptors on the host cell. Following entry, single-stranded viral RNA is converted to double-stranded DNA by reverse transcriptase and is randomly but stably integrated into the infected cell genome DNA. However, in order to be integrated, the cells must be dividing and proliferating (DG Miller, et al., Molecular and Cellular Biology, 10, 8, 4239, 1990). The integrated retroviral gene is called a provirus.
- Retrovirus gene in this case A retrovirus vector is obtained by recombination of the gene with an exogenous gene (AD Mi11er, Currrent Toicsin Microbiology and Immu nology, 158.1, 1992).
- retroviral vectors especially MoMLV vectors, and many improvements have been made in their safety, and no major problems have occurred to date.
- the integration of the target cell into the genomic DNA is random, and the property that the mouth terminal repeat (LTR), which is a part of the viral gene, has a promotion activity for gene expression. It has been known.
- Herpesvirus vectors are expected to be vectors that can transfer foreign genes into neurons (TD Pallell a. Eta 1., Mo 1. Ce 11 1. Biol.. 8, 457 , 1988), however, development is not progressing at present because the virus itself is very large and the genome size of virus itself is as large as 150 kb.
- the HIV vector was developed as a vector that allows specific transduction of ⁇ 04-positive lymphocytes due to the host characteristics of the virus itself (T. Shimada, eta 1..J.C). lin. Invest., 88, 1043. 1991). Lymphocytes are used for gene therapy for innate immunodeficiency disease, AIDS, ⁇ , etc. Therefore, the usefulness of HIV vectors is highly anticipated. The biggest drawback of HIV vectors is the possibility of contamination with wild strains, but if these are resolved, they may be used for in vivo gene therapy by intravascular administration.
- Adenovirus vectors have recently received the most attention because they can transfer genes into non-dividing cells and can easily concentrate vectors to the order of 10.sup.10. Recent studies have shown that this adenovirus vector can transduce genes into airway epithelial cells, hepatocytes, muscular cells, etc. at a high rate in ViV0 (LD LaVrer0, etal. , Hum. Gene Therapy, 1.241. 1990, B. Quintin, Proc. Natl. Acad. Sci. USA, 89, 2581. 1992). On the other hand, this vector has the essential property that foreign genes are not integrated into genomic DNA when introduced into cells. In a month, the effect of introducing a gene is lost.
- the AAV (Ad eno-associated virus) vector requires that the foreign gene be integrated into the genomic DNA of the target cell, has no pathogenicity, and has no cytotoxicity (N. Muzyczka, Currrent Toicsin Microbiologic and Immu). nolo gy, 158, 97. 199 2) Furthermore, the ITR (Inverted Termina 1 Reeat) required for packaging into viral particles and integration of the gene into the genomic DNA has no promotional activity for gene expression, so it is suitable for the purpose. By setting a suitable internal promoter, it is possible to turn on / off gene expression and use a tissue-specific promoter, and at the same time, it has a broad host range and can respond to various target cell Z diseases.
- a freeze-drying method that maintains high gene transfer efficiency by using only low-molecular substances already used as pharmaceutical additives as additives without containing components that can serve as an immunogen, such as gelatin, is used.
- the present invention provides a recombinant virus vector comprising one or more additives selected from arginine, glutamic acid (or its sodium salt), serine, glucose, inositol, lactose, mannitol, sorbitol, trehalose and xylose.
- the present invention provides a method for producing a gene-introduced preparation, which comprises adding and freeze-drying.
- the present invention also provides a gene transfer preparation produced by the above method.
- Figure 1 is a graph showing the efficiency of gene transfer when various additives were added at a concentration of 5%.
- FIG. 2 is a graph showing gene transfer efficiency when various additives were added at 2.5% and 5% concentrations.
- FIG. 3 is a graph showing the efficiency of gene transfer when two kinds of additives at a concentration of 2.5% were added in combination.
- the viral vector that can be used in the method of the present invention is the above-mentioned Mo MLV (mouse Any virus vector used for gene therapy, such as a leukemia virus vector, a herpes virus vector, an adenovirus vector, an adeno-associated virus (AAV) vector, and a human immunodeficiency virus (HIV) vector may be used.
- a virus vector used for gene therapy, such as a leukemia virus vector, a herpes virus vector, an adenovirus vector, an adeno-associated virus (AAV) vector, and a human immunodeficiency virus (HIV) vector may be used.
- a viral vector is dissolved in a medium such as a DMEM medium or PBS to prepare a viral vector stock solution.
- the concentration of the viral vector stock solution may be any.
- the method of the present invention can be achieved by adding an additive to the above-mentioned stock solution of the virus vector and freeze-drying the same.
- Additives that can be used in the present invention are preferably substances having low immunogenicity, and are low-molecular-weight amino acids and their derivatives, sugars and their derivatives.
- amino acid and its derivative As the amino acid and its derivative, arginine, glutamic acid (or its sodium salt) and serine are preferable, and glutamic acid or its sodium salt is particularly preferable.
- glucose, inositol, lactose, mannitol, sorbitol, trehalose and xylose are preferred, and dalcose is most preferred.
- one or more selected from these amino acids and sugars can be freely combined to be used as an additive. You can choose from a combination of only amino acids, a combination of only sugars, and a combination of amino acids and sugars.
- the combination of sodium glutamate and glucose is most preferred because it retains high gene transfer efficiency (virus vector titer).
- the weight ratio of each additive selected from amino acids and sugars to the vector solution is about 1 to about 10%, preferably about 1.5 to about 7%, respectively, and both are most preferable. Is about 1.5 to about 5%.
- virus vector solution is preferably isotonic, so that the osmotic pressure can be adjusted by adding a buffer to the virus vector solution.
- the thus-obtained diluent vector solution containing various additives is freeze-dried. Freeze-drying can be performed by a known method. For example, after freeze-drying with liquid nitrogen, it can be performed by a freeze-dryer (manufactured by Fin Aqua).
- the lyophilized transgenic product is sealed in vials and stored, preferably at low temperature, until use.
- the gene transfer preparation of the present invention can be regenerated with water at the time of use.
- the virus vector regenerated with water maintained high t and gene transfer efficiency.
- a gene transfer preparation that does not contain components that can serve as an immunogen, such as gelatin, and that uses only low-molecular-weight substances, which have already been used as pharmaceutical additives, as additives, keeps gene transfer efficiency high. Can be obtained.
- the gene-introduced preparation of the present invention is easy to store, can maintain a stable titer, can be used for any virus vector preparation, and its application range is extremely wide.
- a 9 cm diameter cell culture dish was seeded with PA311 / ⁇ -19 (provided by Nippon Medical University professor Shimada), which is a cell producing the recombinant MoML V vector containing the neomycin resistance gene. Incubate in normal conditions (37 ° C, carbon dioxide concentration 5%) up to 80% confluent in DMEM (Gibco) containing 10% serum (Gibco). After the cells are cultured to 80% confluence, the medium is replaced. After 12 hours, the medium containing the recombinant MoMLV vector is recovered and used as the vector stock solution.
- Example 2 Preparation of recombinant MoML V vector solution and lyophilization
- Example 3 Recombinant MoMLV vector titer ( ⁇ gene transfer efficiency) Measurement method
- 3T3 cells (Dainippon Pharmaceutical Co., Ltd.) are seeded on a cell culture dish with a diameter of 6 cm, and up to 80% confluent in DMEM (Gibco) containing 10% fetal serum (Gibco). After c cells cultured under normal conditions (37% carbon dioxide concentration 5%) were cultured to 80% confluence, they were used for titer measurement.
- Distilled water for injection (manufactured by Otsuka Pharmaceutical Co., Ltd.) was added to the freeze-dried product obtained in Example 2 to prepare a vector resuspension having the same volume as that before freeze-drying.
- the resulting vector resuspension (10 u ⁇ ) and DMEM990 ⁇ containing 10% fetal bovine serum were added and mixed to prepare a vector solution for titer measurement.
- the culture medium of 3.3 cells cultured to 80% confluent was removed, and 1000 1 of a vector solution for titer measurement was added thereto, followed by culturing under ordinary conditions.
- Figure 1 shows the results when various additives were used at a concentration of 5% '. Higher titers were found for glucose, sodium glutamate, mannitol and trehalose. Figures 2 and 3 show the results when these were added at 2.5% and when two types of additives were mixed and used. From the above results, it was clarified that a freeze-dried virus vector having a high titer can be obtained by using glucose and sodium glutamate as additives.
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/913,592 US5869306A (en) | 1995-03-17 | 1996-03-15 | Gene transfer preparation |
EP96906024A EP0872249A4 (en) | 1995-03-17 | 1996-03-15 | GENE TRANSFER PREPARATION |
AU49544/96A AU4954496A (en) | 1995-03-17 | 1996-03-15 | Gene transfer preparation |
JP52827496A JP3193057B2 (ja) | 1995-03-17 | 1996-03-15 | 遺伝子導入製剤 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP5926195 | 1995-03-17 | ||
JP7/59261 | 1995-03-17 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1996029096A1 true WO1996029096A1 (fr) | 1996-09-26 |
Family
ID=13108262
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1996/000652 WO1996029096A1 (fr) | 1995-03-17 | 1996-03-15 | Preparation de transfert genique |
Country Status (4)
Country | Link |
---|---|
US (1) | US5869306A (ja) |
EP (1) | EP0872249A4 (ja) |
AU (1) | AU4954496A (ja) |
WO (1) | WO1996029096A1 (ja) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
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US6258362B1 (en) | 1998-04-24 | 2001-07-10 | Cantab Pharmaceuticals Research Ltd | Stabilization of herpes virus preparations |
US7052875B1 (en) * | 1998-05-22 | 2006-05-30 | Sumitomo Pharmaceutical Company, Limited | Stable gene preparations |
JP2007001866A (ja) * | 2004-06-14 | 2007-01-11 | Ishihara Sangyo Kaisha Ltd | 膜融合活性のある不活性化ウイルスエンベロープの凍結乾燥組成物 |
JP2011516545A (ja) * | 2008-04-09 | 2011-05-26 | ビロメッド カンパニー, リミテッド | プラスミドdnaの発現増強用凍結乾燥dna製剤 |
WO2020026968A1 (ja) * | 2018-07-30 | 2020-02-06 | 株式会社遺伝子治療研究所 | Aavベクターによる遺伝子発現を増強する方法 |
Families Citing this family (11)
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ZA973642B (en) * | 1996-04-26 | 1997-11-25 | Merck & Co Inc | DNA vaccine formulations. |
US6225289B1 (en) | 1998-12-10 | 2001-05-01 | Genvec, Inc. | Methods and compositions for preserving adenoviral vectors |
ES2327609T3 (es) * | 2000-06-01 | 2009-11-02 | University Of North Carolina At Chapel Hill | Procedimientos y compuestos para controlar la liberacion de vectores de parvovirus reconbinantes. |
US7013940B2 (en) * | 2001-04-19 | 2006-03-21 | Michelin Recherche Et Technique S.A. | Device for attenuating cavity noise in a tire and wheel |
US20030153065A1 (en) * | 2002-01-14 | 2003-08-14 | Genvec, Inc. | Composition and method for maintaining non-enveloped viral vectors |
US7398911B2 (en) * | 2003-12-16 | 2008-07-15 | The Boeing Company | Structural assemblies and preforms therefor formed by friction welding |
ATE495760T1 (de) * | 2004-06-14 | 2011-02-15 | Ishihara Sangyo Kaisha | Gefriergetrocknete zusammensetzung aus einer inaktivierten virushülle mit membranfusionsaktivität |
CN101312742B (zh) * | 2005-09-16 | 2012-07-25 | 梅瑞尔有限公司 | 用于冷冻干燥的疫苗的稳定剂 |
CN104984352A (zh) * | 2005-11-21 | 2015-10-21 | 圣诺菲·帕斯图尔有限公司 | 重组病毒的稳定制剂 |
DK2741740T3 (en) | 2011-08-12 | 2017-06-06 | Merial Inc | VACUUM-SUPPORTED CONSERVATION OF BIOLOGICAL PRODUCTS, IN PARTICULAR OF VACCINES |
TWI690322B (zh) | 2012-10-02 | 2020-04-11 | 法商傳斯堅公司 | 含病毒的調配物及其使用 |
Citations (1)
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WO1995019427A1 (en) * | 1994-01-12 | 1995-07-20 | Genetic Therapy, Inc. | Purification of retroviral vectors |
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FR2076787A5 (en) * | 1970-01-28 | 1971-10-15 | Merieux Inst | Lyophilisation stabiliser - for viruses contg potassium phosphate lactose and albumin |
WO1990011359A1 (en) * | 1989-03-20 | 1990-10-04 | Whitehead Institute For Biomedical Research | Intracellular method of inhibiting hiv in mammalian cells |
US5292653A (en) * | 1989-09-27 | 1994-03-08 | Novagene, Inc. | Equine herpesvirus 1 tk mutants |
GB9305759D0 (en) * | 1993-03-19 | 1993-05-05 | Medical Research Council And T | Hiv therapy method and agents |
CA2158935A1 (en) * | 1993-10-12 | 1995-04-20 | Chiron Viagene, Inc. | Methods for preserving recombinant viruses |
US5681746A (en) * | 1994-12-30 | 1997-10-28 | Chiron Viagene, Inc. | Retroviral delivery of full length factor VIII |
-
1996
- 1996-03-15 US US08/913,592 patent/US5869306A/en not_active Expired - Fee Related
- 1996-03-15 EP EP96906024A patent/EP0872249A4/en not_active Withdrawn
- 1996-03-15 WO PCT/JP1996/000652 patent/WO1996029096A1/ja not_active Application Discontinuation
- 1996-03-15 AU AU49544/96A patent/AU4954496A/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO1995019427A1 (en) * | 1994-01-12 | 1995-07-20 | Genetic Therapy, Inc. | Purification of retroviral vectors |
Non-Patent Citations (3)
Title |
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Chemical Abstracts Service (C A S); 1 January 1994 (1994-01-01), KOTANI HITOSHI, ET AL: "IMPROVED METHODS OF RETROVIRAL VECTOR TRANSDUCTION AND PRODUCTION FOR GENE THERAPY", XP002948738, Database accession no. 121:223170Y * |
See also references of EP0872249A4 * |
TOMONOKAI OF NATIONAL INSTITUTE OF HEALTH, "Rev. ed. 2 Experimental Virology General Description", (1973), MARUZEN, p. 53-59, Section of "5.2 Freeze-Drying". * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
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US6258362B1 (en) | 1998-04-24 | 2001-07-10 | Cantab Pharmaceuticals Research Ltd | Stabilization of herpes virus preparations |
US7052875B1 (en) * | 1998-05-22 | 2006-05-30 | Sumitomo Pharmaceutical Company, Limited | Stable gene preparations |
JP2007001866A (ja) * | 2004-06-14 | 2007-01-11 | Ishihara Sangyo Kaisha Ltd | 膜融合活性のある不活性化ウイルスエンベロープの凍結乾燥組成物 |
JP2011516545A (ja) * | 2008-04-09 | 2011-05-26 | ビロメッド カンパニー, リミテッド | プラスミドdnaの発現増強用凍結乾燥dna製剤 |
WO2020026968A1 (ja) * | 2018-07-30 | 2020-02-06 | 株式会社遺伝子治療研究所 | Aavベクターによる遺伝子発現を増強する方法 |
JPWO2020026968A1 (ja) * | 2018-07-30 | 2021-08-12 | 株式会社遺伝子治療研究所 | Aavベクターによる遺伝子発現を増強する方法 |
Also Published As
Publication number | Publication date |
---|---|
EP0872249A1 (en) | 1998-10-21 |
US5869306A (en) | 1999-02-09 |
EP0872249A4 (en) | 2001-10-24 |
AU4954496A (en) | 1996-10-08 |
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