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WO1988008450A1 - Therapie genetique pour troubles du metabolisme - Google Patents

Therapie genetique pour troubles du metabolisme Download PDF

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Publication number
WO1988008450A1
WO1988008450A1 PCT/US1988/001365 US8801365W WO8808450A1 WO 1988008450 A1 WO1988008450 A1 WO 1988008450A1 US 8801365 W US8801365 W US 8801365W WO 8808450 A1 WO8808450 A1 WO 8808450A1
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WO
WIPO (PCT)
Prior art keywords
recombinant
stem cell
cell
cells
heterologous gene
Prior art date
Application number
PCT/US1988/001365
Other languages
English (en)
Inventor
Birdwell Finlayson
Ammon Broughton Peck
Original Assignee
Birdwell Finlayson
Ammon Broughton Peck
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 Birdwell Finlayson, Ammon Broughton Peck filed Critical Birdwell Finlayson
Publication of WO1988008450A1 publication Critical patent/WO1988008450A1/fr

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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
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/44—Oxidoreductases (1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/51—Lyases (4)
    • 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
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • 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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/52—Genes encoding for enzymes or proenzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y102/00—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2)
    • C12Y102/03—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2) with oxygen as acceptor (1.2.3)
    • C12Y102/03004—Oxalate oxidase (1.2.3.4)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y107/00—Oxidoreductases acting on other nitrogenous compounds as donors (1.7)
    • C12Y107/03—Oxidoreductases acting on other nitrogenous compounds as donors (1.7) with oxygen as acceptor (1.7.3)
    • C12Y107/03003—Factor-independent urate hydroxylase (1.7.3.3), i.e. uricase
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y401/00—Carbon-carbon lyases (4.1)
    • C12Y401/01—Carboxy-lyases (4.1.1)
    • C12Y401/01002—Oxalate decarboxylase (4.1.1.2)
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

Definitions

  • Oxalobacter formigenes is a recently described oxalate-degrading anaerobic bacterium which, inhabits the rumen of animals as well as the colon of man (Allison, M.J., 1985, Arch. Microbiol. 141:1-7).
  • O. formigenes OxB is a strain that grows in media containing oxalate as the sole metabolic substrate. Other substrates do not- appear to support its growth. The degradation of oxalate catalyzed by the bacterial enzyme results in CO- and formic acid production (Allison, M.J. , supra) .
  • the invention is also directed to recombinant stem cell progeny which express heterologous immunoglobulin genes. 3.1. DEFINITIONS
  • CFU colony-forming unit A cell which is capable of producing a colony of progeny cells in soft agar medium.
  • Concanavalin A (Con A) (Q Q) .
  • B Mixed leukocyte culture (MLC) responses of spleen cells against gamma- irradiated B10.SAA48 (
  • HSC hematopoietic stem cells
  • Any viral vector capable of stably transferring the metabolase gene to the mammalian stem cell without significant undesirable side effects can be used in accordance with this embodiment of the invention.
  • Such vectors include but are not limited to those derived from parvoviruses such as adeno-associated viruses (such as described in Sections 6, 7, infra) , papovaviruses such as bovine papilloma viruses, herpes simplex viruses, retroviruses, etc. (See e.g. , Tratschin, J.-D., et al., 1985, Mol. Cell. Biol. 5:3251; Campo, M.S., 1985, in DNA Cloning: A Practical Approach, Vol.
  • the recombinant cell population can be substantially enriched, or further enriched, for the desire stem cell population before introduction into the host, by procedures such as fluorescent-activated cell sorting on th basis of cell size or antibody-binding, or antibody depletion mediated by complement (see Section 5.1.2.1, supra) .
  • Antibody fragments which contain the idiotype of the molecule can be generated by known techniques.
  • such fragments include but are not limited to: the F(ab') fragment which can be produced by pepsin digestion of the antibody molecule; the Fab' fragments which can be generated by reducing the disulfide bridges of the F(ab') 2 fragment, and the Fab fragments which can be generated by treating the antibody molecule with papain and a reducing agent.
  • Antibodies reactive with a metabolase can be used in immunoassays to detect, localize, or measure the amount of the metabolase protein in a sample.
  • the immunoassays which can be used include but are not limited to competitive and non-competitive assay systems using techniques such as radioimmunoassays, ELISA (enzyme linked immunosorbent assay) , "sandwich” immunoassays, precipitin reactions, gel diffusion precipitin reactions, immunodiffusion assays, agglutination assays, complement-fixation assays, immunoradiometric assays, fluorescent immunoassays, protein A immunoassays, and immunoelectrophoresis assays, to name but a few.
  • a 1.8 kilobase pair (kb) DNA fragment containing the SV40 early promoter region and the bacterial neomycin resistance gene (Neo) was inserted into the AAV deletion mutant dl52-91, to generate the recombinant dl52-91/neo.
  • 5 micrograms of dl52-91/neo plasmid DNA and 0.5 micrograms of ins96/lambda-M plasmid DN were cotransfected into adenovirus-2 (AD-2) infected KB cells or HeP-2 cells by using DEAE-dextran (Hermonat, P.L. and Muzyczka, N.
  • the examples sections detailed herein are directed to a demonstration that a bacterial-derived oxalase gene, when transferred to a mammalian (specifically, murine) host via the hematopoietic system, can lower the concentration in the circulatory system of the metabolic product oxalate. This has potential value in methods of treatment or prevention of kidney stone formation and other disorders of excess oxalate, as provided for by the present invention.
  • oxalase activity by recombinant stem cells and their progeny can be demonstrated by detection of CO release due to substrate (oxalate) degradation. CO is released into the atmosphere by . . . . . 14 acidification and, if radioactive (e.g. , C-labeled) , will darken vicinal photographic film.
  • radioactive e.g. , C-labeled
  • B10.BR/cd cells responded strongly to Con A and LPS stimulation, thus demonstrating immunocompetence of the
  • T cell engraftment hosts -examined at day 60 post-engraftment remained tolerant to host cells but responded to donor and third-party cells. Furthermore, at day 60 all of the splenocytes serotyped as host cells.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Physics & Mathematics (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

Cellules souches mammifères recombinantes contenant un gène hétérologue codant pour une enzyme qui modifie ou dégrade le métabolite, et utilisation de telles cellules dans le traitement ou la prévention d'une maladie, ou d'un trouble des mammifères résultant d'une concentration ou d'une accumulation accrues d'un métabolite. L'invention se rapporte également à des compositions utiles pour la production de telles cellules souches mammifères recombinantes. Les cellules souches recombinantes ou leur descendance sont introduites dans ou sur l'hôte, où elles prolifèrent pour produire une descendance de cellules souches exprimant l'enzyme hétérologue capable de modifier ou de dégrader le métabolite in vivo. Dans un mode de réalisation spécifique, un gène hétérologue codant pour une enzyme capable de transformer par métabolisme de l'oxalate, peut être exprimé dans des cellules souches recombinantes afin de traiter ou d'empêcher la formation de calculs du rein. Dans un autre mode de réalisation, une enzyme hétérologue modifiant ou dégradant l'acide urique peut être exprimée, afin de traiter ou de prévenir la formation de calculs ou la goutte.
PCT/US1988/001365 1987-05-01 1988-04-26 Therapie genetique pour troubles du metabolisme WO1988008450A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US4491887A 1987-05-01 1987-05-01
US044,918 1987-05-01
US180,734 1988-04-12

Publications (1)

Publication Number Publication Date
WO1988008450A1 true WO1988008450A1 (fr) 1988-11-03

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Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2221910A (en) * 1988-08-17 1990-02-21 Sapporo Breweries DNA encoding a uricase gene
EP0408461A1 (fr) * 1989-07-13 1991-01-16 Sanofi Protéine à activité urate oxydase, gène recombinant codant pour celle-ci, vecteur d'expression, micro-organismes et cellules transformées
FR2649720A1 (en) * 1989-07-13 1991-01-18 Sanofi Sa Recombinant gene which encodes a protein such as urate oxidase
FR2656530A1 (fr) * 1989-12-29 1991-07-05 Sanofi Sa Gene recombinant pour une expression dans les cellules eucaryotes d'une proteine telle que l'urate oxydase.
EP0456640A4 (fr) * 1988-12-13 1991-09-20 Us Health Cellules endotheliales modifiees par genie genetique et utilisation de ces cellules.
WO1992009688A1 (fr) * 1990-11-21 1992-06-11 Massachusetts Institute Of Technology SOURIS A DISLOCATION DE GENE DE MICROGLOBULINE β2
WO1992014824A1 (fr) * 1991-02-25 1992-09-03 Imperial Chemical Industries Plc Oxalate oxydase nouvellement caracterisee et utilisations de celle-ci
WO1992015685A1 (fr) * 1991-03-05 1992-09-17 Rhone Poulenc Agrochimie Production de plantes resistantes aux attaques de sclerotinia sclerotiorum par introduction d'un gene codant pour une oxalate oxydase
EP0457856A4 (en) * 1989-06-13 1992-10-21 The Board Of Directors Of The Leland Stanford Junior University Isolation growth and differentiation of human muscle cells
WO1993009239A1 (fr) * 1991-11-08 1993-05-13 Research Corporation Technologies, Inc. Vecteurs basaux du virus 2 adeno-apparente
WO1994001139A1 (fr) * 1992-07-13 1994-01-20 Baylor College Of Medicine Ciblage d'une therapie genique somatique en direction des articulations
WO1994013823A1 (fr) * 1992-12-10 1994-06-23 Z. Company S.A. Sequence nucleotidique destinee au traitement du cancer et des infections
WO1996009400A1 (fr) * 1994-09-19 1996-03-28 Systemix, Inc. Procedes permettant de modifier genetiquement des cellules souches hematopoietiques
US5547870A (en) * 1992-11-30 1996-08-20 Zeneca Limited Oxalate decarboxylate
US5635616A (en) * 1995-06-02 1997-06-03 Human Genome Sciences, Inc. Human oxalyl-CoA decarboxylase
WO1997033975A1 (fr) 1996-03-12 1997-09-18 Rhone-Poulenc Rorer S.A. Milieu pour la conservation de materiel biologique
EP0845537A1 (fr) * 1989-08-18 1998-06-03 Chiron Corporation Retrovirus recombinants exprimant une pro-drogue pour le traitement des GVhD
US5792751A (en) * 1992-04-13 1998-08-11 Baylor College Of Medicine Tranformation of cells associated with fluid spaces
US5945273A (en) * 1997-06-03 1999-08-31 Human Genome Sciences, Inc. Human oxalyl-coa decarboxylase
US6261834B1 (en) 1991-11-08 2001-07-17 Research Corporation Technologies, Inc. Vector for gene therapy
EP2457576A1 (fr) 2010-11-29 2012-05-30 Eurochit Danuta Kruszewska Nouvelle souche de Lactobacillus reuteri utile dans la prophylaxie et le traitement médical et vétérinaire
WO2013180585A1 (fr) 2012-05-29 2013-12-05 Danuta Kruszewska Nano-produit comportant lactobacillus reuteri dan080, utile en prophylaxie et en médecine humaine et vétérinaire, et son utilisation médicale
WO2014011901A3 (fr) * 2012-07-11 2014-06-05 Sangamo Biosciences, Inc. Procédés et compositions pour la délivrance d'agents biologiques
US9260752B1 (en) 2013-03-14 2016-02-16 Caribou Biosciences, Inc. Compositions and methods of nucleic acid-targeting nucleic acids
US9885026B2 (en) 2011-12-30 2018-02-06 Caribou Biosciences, Inc. Modified cascade ribonucleoproteins and uses thereof
US10000772B2 (en) 2012-05-25 2018-06-19 The Regents Of The University Of California Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription
US10731181B2 (en) 2012-12-06 2020-08-04 Sigma, Aldrich Co. LLC CRISPR-based genome modification and regulation

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Volume 106, No. 20, issued 25 May 1987 (Columbus, Ohio, USA), CAMPOS et al., "Nodule specific genes in Phaseolus vulgaris", see page 166, column 2, the abstract no. 170031k, Mol Genet. Plant-Microbe Interact, Proc. Int. Symp. 3rd, 1986, 115-117 (Eng). *
JOURNAL OF VIROLOGY, Volume 51, issued August 1984, (Washington D.C., USA), (HERMONAT et al.), "Genetics of Adeno-Associated Virus: Isolation and Preliminary Characterization of Adeno-Associated Virus Type 2 Mutants", see page 329. *
MOLECULAR AND CELLULAR BIOLOGY, Volume 5, issued November 1985, (Washington D.C., USA), (TRATSCHIN et al.), "Adeno-Associated Virus Vector for High-Frequency Integration, Expression, and Rescue of Genes in Mammalian Cells", see page 3251. *
MOLECULAR AND CELLULAR BIOLOGY, Volume 6, issued August 1986, (Washington D.C., USA), (TRATSCHIN et al), "Negative and Positive Regulation in Trans of Gene Expression from Adeno-Associated Virus Vectors in Mammalian Cells by a Viral rep Gene Product", see page 2884. *
NATURE, Volume 310, issued 9 August 1984, (London, England), (WILLIAMS et al.), "Introduction of new genetic material into pluripotent stem cells of the mouse", see pages 476 and 478-480. *
NATURE, Volume 318, issued 14 November 1985, (London, England), (KELLER et al.), "Expression of a foreign gene in myeloid and lymphoid cells derived from multipotent haematopoietic precursors", see pages 153-154. *
NATURE, Volume 320, issued 20 March 1986, (London, England), (HOCK et al), "Retrovirus-mediated transfer and expression of drug resistance genes in human haematopoietic progenitor cells", see pages 276-277. *
VIROLOGY, Volume 162, issued February 1988, (New York, New York), (LAFACE et al.), "Gene Transfer into Hematopoietic Progenitor Cells Mediated by an Adeno-Associated Virus Vector", see pages 483-486. *

Cited By (109)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2221910B (en) * 1988-08-17 1992-11-04 Sapporo Breweries A uricase gene and production of uricase
GB2221910A (en) * 1988-08-17 1990-02-21 Sapporo Breweries DNA encoding a uricase gene
EP0456640A4 (fr) * 1988-12-13 1991-09-20 Us Health Cellules endotheliales modifiees par genie genetique et utilisation de ces cellules.
EP0457856A4 (en) * 1989-06-13 1992-10-21 The Board Of Directors Of The Leland Stanford Junior University Isolation growth and differentiation of human muscle cells
EP0408461A1 (fr) * 1989-07-13 1991-01-16 Sanofi Protéine à activité urate oxydase, gène recombinant codant pour celle-ci, vecteur d'expression, micro-organismes et cellules transformées
FR2649720A1 (en) * 1989-07-13 1991-01-18 Sanofi Sa Recombinant gene which encodes a protein such as urate oxidase
WO1991000909A1 (fr) * 1989-07-13 1991-01-24 Sanofi Proteine a activite urate oxydase, gene recombinant codant pour celle-ci, vecteur d'expression, micro-organismes et cellules transformees
EP0845537A1 (fr) * 1989-08-18 1998-06-03 Chiron Corporation Retrovirus recombinants exprimant une pro-drogue pour le traitement des GVhD
EP1645635A3 (fr) * 1989-08-18 2010-07-07 Oxford Biomedica (UK) Limited Retrovirus recombinants défectifs pour la réplication exprimant un palliatif
FR2656530A1 (fr) * 1989-12-29 1991-07-05 Sanofi Sa Gene recombinant pour une expression dans les cellules eucaryotes d'une proteine telle que l'urate oxydase.
FR2657785A2 (fr) * 1989-12-29 1991-08-09 Sanofi Sa Gene recombinant pour une expression dans les cellules animales d'une proteine telle que l'urate oxydage.
WO1992009688A1 (fr) * 1990-11-21 1992-06-11 Massachusetts Institute Of Technology SOURIS A DISLOCATION DE GENE DE MICROGLOBULINE β2
WO1992014824A1 (fr) * 1991-02-25 1992-09-03 Imperial Chemical Industries Plc Oxalate oxydase nouvellement caracterisee et utilisations de celle-ci
US5866778A (en) * 1991-02-25 1999-02-02 Zeneca Limited Newly characterized oxalate and uses therefor
WO1992015685A1 (fr) * 1991-03-05 1992-09-17 Rhone Poulenc Agrochimie Production de plantes resistantes aux attaques de sclerotinia sclerotiorum par introduction d'un gene codant pour une oxalate oxydase
CN1051576C (zh) * 1991-03-05 2000-04-19 罗纳-普朗克农业化学公司 经引入编码草酸氧化酶的基因生产抗桑条菌核病核盘霉攻击的植物
US5252479A (en) * 1991-11-08 1993-10-12 Research Corporation Technologies, Inc. Safe vector for gene therapy
AU657829B2 (en) * 1991-11-08 1995-03-23 Research Corporation Technologies, Inc. Adeno-associated virus-2 basal vectors
WO1993009239A1 (fr) * 1991-11-08 1993-05-13 Research Corporation Technologies, Inc. Vecteurs basaux du virus 2 adeno-apparente
US6261834B1 (en) 1991-11-08 2001-07-17 Research Corporation Technologies, Inc. Vector for gene therapy
US5792751A (en) * 1992-04-13 1998-08-11 Baylor College Of Medicine Tranformation of cells associated with fluid spaces
WO1994001139A1 (fr) * 1992-07-13 1994-01-20 Baylor College Of Medicine Ciblage d'une therapie genique somatique en direction des articulations
US5547870A (en) * 1992-11-30 1996-08-20 Zeneca Limited Oxalate decarboxylate
WO1994013823A1 (fr) * 1992-12-10 1994-06-23 Z. Company S.A. Sequence nucleotidique destinee au traitement du cancer et des infections
BE1006437A3 (fr) * 1992-12-10 1994-08-30 Company S A Z Sequence nucleotidique destinee au traitement du cancer et des infections.
US6200796B1 (en) 1994-05-18 2001-03-13 Human Genome Sciences, Inc. Human oxalyl-CoA decarboxylase
US6383737B2 (en) 1994-05-18 2002-05-07 Human Genome Sciences, Inc. Human oxalyl-CoA Decarboxylase
WO1996009400A1 (fr) * 1994-09-19 1996-03-28 Systemix, Inc. Procedes permettant de modifier genetiquement des cellules souches hematopoietiques
US5635616A (en) * 1995-06-02 1997-06-03 Human Genome Sciences, Inc. Human oxalyl-CoA decarboxylase
WO1997033975A1 (fr) 1996-03-12 1997-09-18 Rhone-Poulenc Rorer S.A. Milieu pour la conservation de materiel biologique
US5945273A (en) * 1997-06-03 1999-08-31 Human Genome Sciences, Inc. Human oxalyl-coa decarboxylase
EP2457576A1 (fr) 2010-11-29 2012-05-30 Eurochit Danuta Kruszewska Nouvelle souche de Lactobacillus reuteri utile dans la prophylaxie et le traitement médical et vétérinaire
US9885026B2 (en) 2011-12-30 2018-02-06 Caribou Biosciences, Inc. Modified cascade ribonucleoproteins and uses thereof
US11939604B2 (en) 2011-12-30 2024-03-26 Caribou Biosciences, Inc. Modified cascade ribonucleoproteins and uses thereof
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US10711257B2 (en) 2011-12-30 2020-07-14 Caribou Biosciences, Inc. Modified cascade ribonucleoproteins and uses thereof
US10435678B2 (en) 2011-12-30 2019-10-08 Caribou Biosciences, Inc. Modified cascade ribonucleoproteins and uses thereof
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