JP7003232B2 - グルコース依存性の生存率を介して、細菌が固形腫瘍を特異的に標的とすることを可能にする核酸システム - Google Patents
グルコース依存性の生存率を介して、細菌が固形腫瘍を特異的に標的とすることを可能にする核酸システム Download PDFInfo
- Publication number
- JP7003232B2 JP7003232B2 JP2020513887A JP2020513887A JP7003232B2 JP 7003232 B2 JP7003232 B2 JP 7003232B2 JP 2020513887 A JP2020513887 A JP 2020513887A JP 2020513887 A JP2020513887 A JP 2020513887A JP 7003232 B2 JP7003232 B2 JP 7003232B2
- Authority
- JP
- Japan
- Prior art keywords
- nucleic acid
- acid system
- glucose
- promoter
- dna fragment
- 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.)
- Active
Links
- 206010028980 Neoplasm Diseases 0.000 title claims description 166
- 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 title claims description 127
- 239000008103 glucose Substances 0.000 title claims description 126
- 108020004707 nucleic acids Proteins 0.000 title claims description 102
- 150000007523 nucleic acids Chemical class 0.000 title claims description 102
- 102000039446 nucleic acids Human genes 0.000 title claims description 102
- 241000894006 Bacteria Species 0.000 title description 61
- 230000001419 dependent effect Effects 0.000 title description 2
- 230000004083 survival effect Effects 0.000 title description 2
- 239000012634 fragment Substances 0.000 claims description 69
- 230000001580 bacterial effect Effects 0.000 claims description 58
- 239000000729 antidote Substances 0.000 claims description 49
- 108700012359 toxins Proteins 0.000 claims description 44
- 241000588724 Escherichia coli Species 0.000 claims description 38
- 239000002773 nucleotide Substances 0.000 claims description 32
- 125000003729 nucleotide group Chemical group 0.000 claims description 32
- 108090000623 proteins and genes Proteins 0.000 claims description 31
- 238000011144 upstream manufacturing Methods 0.000 claims description 31
- 239000003053 toxin Substances 0.000 claims description 27
- 231100000765 toxin Toxicity 0.000 claims description 27
- 230000008685 targeting Effects 0.000 claims description 19
- 230000035897 transcription Effects 0.000 claims description 18
- 238000013518 transcription Methods 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 14
- 241000660147 Escherichia coli str. K-12 substr. MG1655 Species 0.000 claims description 11
- 229960005091 chloramphenicol Drugs 0.000 claims description 6
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 claims description 6
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 3
- 241000607142 Salmonella Species 0.000 claims description 3
- 238000012258 culturing Methods 0.000 claims description 3
- 241000607768 Shigella Species 0.000 claims description 2
- 101150106096 gltA gene Proteins 0.000 claims description 2
- 101150042350 gltA2 gene Proteins 0.000 claims description 2
- 101150037435 tnaB gene Proteins 0.000 claims description 2
- 108020004414 DNA Proteins 0.000 description 52
- 241000699670 Mus sp. Species 0.000 description 43
- 210000004185 liver Anatomy 0.000 description 33
- 210000001519 tissue Anatomy 0.000 description 27
- 238000011580 nude mouse model Methods 0.000 description 26
- 241000699660 Mus musculus Species 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 25
- 241000699666 Mus <mouse, genus> Species 0.000 description 20
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 16
- 201000010099 disease Diseases 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 239000006142 Luria-Bertani Agar Substances 0.000 description 13
- 238000010253 intravenous injection Methods 0.000 description 13
- 239000002609 medium Substances 0.000 description 13
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 12
- 239000002953 phosphate buffered saline Substances 0.000 description 12
- 101150043283 ccdA gene Proteins 0.000 description 11
- 210000000952 spleen Anatomy 0.000 description 10
- 229920001817 Agar Polymers 0.000 description 9
- 239000008272 agar Substances 0.000 description 9
- 210000000056 organ Anatomy 0.000 description 9
- 210000000349 chromosome Anatomy 0.000 description 8
- 231100000433 cytotoxic Toxicity 0.000 description 8
- 230000001472 cytotoxic effect Effects 0.000 description 8
- 230000012010 growth Effects 0.000 description 8
- 239000003550 marker Substances 0.000 description 8
- 206010009944 Colon cancer Diseases 0.000 description 7
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 7
- 230000002950 deficient Effects 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 108091081024 Start codon Proteins 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 101150102092 ccdB gene Proteins 0.000 description 6
- 230000004614 tumor growth Effects 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 206010021143 Hypoxia Diseases 0.000 description 4
- 230000001093 anti-cancer Effects 0.000 description 4
- 229940041181 antineoplastic drug Drugs 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 210000002216 heart Anatomy 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 210000003578 bacterial chromosome Anatomy 0.000 description 3
- 241001641064 bacterium 122 Species 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000001332 colony forming effect Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002550 fecal effect Effects 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 238000002626 targeted therapy Methods 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 108700026220 vif Genes Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 206010024652 Liver abscess Diseases 0.000 description 2
- 101710120037 Toxin CcdB Proteins 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000005757 colony formation Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 1
- 241000023308 Acca Species 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 101100287449 Bacillus subtilis (strain 168) fruK gene Proteins 0.000 description 1
- 208000034309 Bacterial disease carrier Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 238000000729 Fisher's exact test Methods 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L L-glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010000269 abscess Diseases 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940075522 antidotes Drugs 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000003139 biocide Substances 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 101150063520 fruB gene Proteins 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028744 lysogeny Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- -1 sdhADC Proteins 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000005909 tumor killing Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/21—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Pseudomonadaceae (F)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/24—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
- C07K14/245—Escherichia (G)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/28—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Vibrionaceae (F)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/32—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Bacillus (G)
-
- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- 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
- C12N15/635—Externally inducible repressor mediated regulation of gene expression, e.g. tetR inducible by tetracyline
-
- 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
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- 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
- C12N2810/55—Vectors comprising as targeting moiety peptide derived from defined protein from bacteria
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/185—Escherichia
- C12R2001/19—Escherichia coli
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Description
112:矢印
120:薬物送達システム
122:細菌
124:抗癌薬
330:肝臓切片
Claims (17)
- 細菌株に導入されて、遺伝子操作された細菌株を生成する核酸システムであって、
前記遺伝子操作された細菌株を死滅させる毒素を発現する毒素遺伝子をコードする第1のDNA断片と、
前記毒素を無効にする解毒剤を発現する解毒剤遺伝子をコードする第2のDNA断片と、
グルコースが前記解毒剤遺伝子の転写を抑制するように、前記解毒剤遺伝子の前記転写を制御する第1のプロモーターと、
前記毒素遺伝子の構成的発現を引き起こす第1の構成的プロモーターと、を含み、
前記第2のDNA断片は、0.424mMよりも低い濃度のグルコース環境で転写されるが、1.22mMよりも高い濃度のグルコース環境では転写されない、核酸システム。 - 前記第1のプロモーターは、前記第2のDNA断片のすぐ上流に位置する、請求項1に記載の核酸システム。
- 前記第1の構成的プロモーターは、前記第1のDNA断片のすぐ上流に位置する、請求項1~2のいずれか1項に記載の核酸システム。
- 前記第1のプロモーターは、lacプロモーター、gltAプロモーター、sdhADCプロモーター及びtnaBプロモーターからなる群から選択される、請求項1~3のいずれか1項に記載の核酸システム。
- 一対の前記毒素と前記解毒剤は、CcdB-CcdA対、AvrRxo1-Arc1対、Hha-TomB対、及びPaaA2-ParE2対からなる群から選択される、請求項1~4のいずれか1項に記載の核酸システム。
- 前記第1のDNA断片は、配列番号1に示され、前記第2のDNA断片は、配列番号2に示される、請求項1~5のいずれか1項に記載の核酸システム。
- 前記第1のプロモーターは、配列番号3に示される、請求項1~6のいずれか1項に記載の核酸システム。
- 5~6個のヌクレオチドからなり、前記第2のDNA断片のすぐ上流に位置する前記遺伝子操作された細菌株の元の5~6個のヌクレオチドを置き換えるランダム配列をさらに含む、請求項1~7のいずれか1項に記載の核酸システム。
- 前記ランダム配列は、GCCTT又はTGTCTである、請求項8に記載の核酸システム。
- クロラムフェニコール耐性カセットをコードする第3のDNA断片をさらに含み、
前記第3のDNA断片は、配列番号4に示される、請求項1~9のいずれか1項に記載の核酸システム。 - 前記細菌株は、大腸菌、サルモネラ菌及び赤痢菌からなる群から選択される、請求項1~10のいずれか1項に記載の核酸システム。
- 前記細菌株は、大腸菌MG1655である、請求項1~11のいずれか1項に記載の核酸システム。
- 配列番号7又は配列番号8に示される、請求項1~12のいずれか1項に記載の核酸システム。
- 遺伝子操作された細菌株を構築する方法であって、
前記遺伝子操作された細菌株を死滅させる毒素を発現する毒素遺伝子をコードする第1のDNA断片と、
前記毒素を無効にする解毒剤を発現する解毒剤遺伝子をコードする第2のDNA断片と、
グルコースが前記解毒剤遺伝子の転写を抑制するように、前記解毒剤遺伝子の前記転写を制御する第1のプロモーターと、
前記毒素遺伝子の構成的発現を引き起こす第1の構成的プロモーターと、
を含む核酸システムを、細菌株に挿入することと、
前記核酸システムを含む前記遺伝子操作された細菌株のクローンを培養することと、
グルコースの非存在下で増殖するが1mM以上の濃度のグルコースの存在下では増殖しない前記クローンを選択することにより、固形腫瘍を標的とする前記遺伝子操作された細菌株を取得することと、を含む、方法。 - 5~6個のヌクレオチドからなるランダム配列を挿入して、前記第2のDNA断片のすぐ上流に位置する天然ヌクレオチドを置き換えることによって、前記核酸システムのランダムライブラリを生成することをさらに含む、請求項14に記載の方法。
- 0mMのグルコース濃度で増殖するが、5mMのグルコース濃度では増殖しない前記クローンは、前記腫瘍を標的とする前記遺伝子操作された細菌株として選択される、請求項14~15のいずれか1項に記載の方法。
- 前記核酸システムは、請求項1~13のいずれか1項に記載の核酸システムである、請求項14~16のいずれか1項に記載の方法。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/CN2017/101069 WO2019047166A1 (en) | 2017-09-08 | 2017-09-08 | NUCLEIC ACID SYSTEMS THAT ALLOW BACTERIA TO SPECIFICALLY TARGET SOLID TUMORS THROUGH GLUCOSE DEPENDENT VIABILITY |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2020533978A JP2020533978A (ja) | 2020-11-26 |
JP7003232B2 true JP7003232B2 (ja) | 2022-02-04 |
Family
ID=65633589
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020513887A Active JP7003232B2 (ja) | 2017-09-08 | 2017-09-08 | グルコース依存性の生存率を介して、細菌が固形腫瘍を特異的に標的とすることを可能にする核酸システム |
JP2020513883A Active JP7102512B2 (ja) | 2017-09-08 | 2018-08-14 | 腫瘍を標的とし癌を治療するための細菌 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020513883A Active JP7102512B2 (ja) | 2017-09-08 | 2018-08-14 | 腫瘍を標的とし癌を治療するための細菌 |
Country Status (7)
Country | Link |
---|---|
US (3) | US11458172B2 (ja) |
EP (2) | EP3679142A4 (ja) |
JP (2) | JP7003232B2 (ja) |
CN (3) | CN111278978B (ja) |
MY (2) | MY195280A (ja) |
SG (2) | SG11202001797TA (ja) |
WO (2) | WO2019047166A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019047166A1 (en) * | 2017-09-08 | 2019-03-14 | New Portal Limited | NUCLEIC ACID SYSTEMS THAT ALLOW BACTERIA TO SPECIFICALLY TARGET SOLID TUMORS THROUGH GLUCOSE DEPENDENT VIABILITY |
US20240082350A1 (en) * | 2019-10-11 | 2024-03-14 | Linnane Pharma Ab | Vibrio cholerae protein for use against cancer |
WO2022006748A1 (en) * | 2020-07-07 | 2022-01-13 | New Portal Limited | Genetically engineered live bacteria and methods of constructing the same |
CN114073777A (zh) * | 2020-08-18 | 2022-02-22 | 中国科学院深圳先进技术研究院 | 携带细胞因子或其多核苷酸的细菌靶向载体及其在肿瘤治疗中的应用 |
CN116676324B (zh) * | 2023-07-28 | 2023-10-27 | 四川大学华西医院 | 基于Kil蛋白构建释放抗肿瘤效应蛋白的系统及方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012087483A1 (en) | 2010-11-24 | 2012-06-28 | The Arizona Board Of Regents For And On Behalf Of Arizona State University | Recombinant bacterium comprising a toxin/antitoxin system |
WO2015118541A1 (en) | 2014-02-05 | 2015-08-13 | Gavish-Galilee Bio Applications Ltd | A genetic system for generating conditionally inactivated or attenuated bacteria |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ237688A (en) | 1990-04-19 | 1993-01-27 | Res Dev Foundation | Antibody-cytotoxic immunoconjugate-containing compositions and cancer treatment |
US5478804A (en) | 1990-09-19 | 1995-12-26 | The Salk Institute For Biological Studies | Treatment of tumorigenic pathophysiological conditions with FGF-cytoxic conjugates |
US6645490B2 (en) * | 1998-03-02 | 2003-11-11 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Chimeric proteins with cell-targeting specificity and apoptosis-inducing activities |
CA2327387C (en) * | 1998-05-07 | 2012-07-03 | Gx Biosystems A/S | Cytotoxin-based biological containment |
GB9916810D0 (en) * | 1999-07-16 | 1999-09-22 | Cancer Res Campaign Tech | Killing cells |
NZ518354A (en) | 1999-10-04 | 2005-02-25 | Vion Pharmaceuticals Inc | Compositions and methods for tumor-targeted delivery of effector molecules |
CA2435956C (en) * | 2001-02-23 | 2012-07-10 | Universite Libre De Bruxelles | Method for the selection of recombinant clones comprising a sequence encoding an antidote protein to toxic molecule |
JP2008504822A (ja) | 2004-06-29 | 2008-02-21 | アンチキャンサー インコーポレーテッド | 癌選択的栄養要求株 |
TW200946677A (en) | 2008-02-05 | 2009-11-16 | Aeterna Zentaris Gmbh | Recombinant bacteria with E. coli hemolysin secretion system and increased expression and/or secretion of H1yA, process of manufacturing and uses thereof |
JP5754648B2 (ja) | 2008-06-25 | 2015-07-29 | バキシオン セラピューティクス,リミテッド ライアビリティ カンパニー | 制御された遺伝子自殺機序組成物及び方法 |
US20120027674A1 (en) | 2010-07-27 | 2012-02-02 | Baylor Research Institute | Il-18 receptor as a novel target of regulatory t cells in cancer |
PT2726599T (pt) * | 2011-06-30 | 2018-06-25 | Exxonmobil Res & Eng Co | Regulação de genes de toxinas e antitoxinas para contenção biológica |
EP2543720A1 (en) * | 2011-07-07 | 2013-01-09 | Delphi Genetics | Genetically modified phage and use thereof |
EP2570134A1 (en) * | 2011-09-15 | 2013-03-20 | De la Cueva-Mendez, Guillermo | Systems and methods for diminishing cell growth and including selective killing of target cells |
US9127284B2 (en) * | 2012-05-04 | 2015-09-08 | The University Of Hong Kong | Modified bacteria and their uses thereof for the treatment of cancer or tumor |
CN104498418B (zh) | 2014-11-14 | 2017-11-17 | 扬州大学 | 一种基因调控延迟减毒和提高表达外源抗原猪霍乱沙门氏菌载体的构建方法 |
DK3234146T3 (da) * | 2014-12-16 | 2019-08-05 | Cloneopt Ab | Selektiv optimering af et ribosombindingssted til proteinproduktion |
CA2971876A1 (en) | 2014-12-22 | 2016-06-30 | Massachusetts Institute Of Technology | Probiotic organisms for diagnosis, monitoring, and treatment of inflammatory bowel disease |
SG11201707025WA (en) | 2015-03-02 | 2017-09-28 | Synlogic Inc | Bacteria engineered to treat diseases that benefit from reduced gut inflammation and/or tightened gut mucosal barrier |
SG10202003100XA (en) | 2015-05-13 | 2020-05-28 | Synlogic Operating Co Inc | Bacteria Engineered to Reduce Hyperphenylalaninemia |
EP3298141A4 (en) | 2015-05-17 | 2019-01-09 | The Medical Research, Infrastructure, And Health Services Fund Of The Tel Aviv Medical Center | COMPOSITIONS AND METHOD FOR THE TREATMENT OF CANCER |
WO2016210373A2 (en) | 2015-06-24 | 2016-12-29 | Synlogic, Inc. | Recombinant bacteria engineered for biosafety, pharmaceutical compositions, and methods of use thereof |
WO2017040719A1 (en) | 2015-08-31 | 2017-03-09 | Synlogic, Inc. | Bacteria engineered to treat disorders in which oxalate is detrimental |
CN106676119B (zh) | 2015-11-05 | 2019-11-12 | 中国科学院微生物研究所 | 细菌无痕遗传操作载体及其构建方法与应用 |
SG11201911031TA (en) | 2017-07-12 | 2020-01-30 | Synlogic Operating Co Inc | Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells |
WO2019047166A1 (en) | 2017-09-08 | 2019-03-14 | New Portal Limited | NUCLEIC ACID SYSTEMS THAT ALLOW BACTERIA TO SPECIFICALLY TARGET SOLID TUMORS THROUGH GLUCOSE DEPENDENT VIABILITY |
CN109649340B (zh) | 2019-01-21 | 2021-09-03 | 广州小鹏汽车科技有限公司 | 基于互联网的洗车方法及洗车机、服务器和车载终端 |
CN110527655B (zh) | 2019-07-15 | 2022-05-20 | 江苏省家禽科学研究所 | 一种鸭源大肠杆菌益生菌菌株及其筛选制备方法与用途 |
-
2017
- 2017-09-08 WO PCT/CN2017/101069 patent/WO2019047166A1/en unknown
- 2017-09-08 SG SG11202001797TA patent/SG11202001797TA/en unknown
- 2017-09-08 MY MYPI2020000961A patent/MY195280A/en unknown
- 2017-09-08 JP JP2020513887A patent/JP7003232B2/ja active Active
- 2017-09-08 EP EP17924042.9A patent/EP3679142A4/en active Pending
- 2017-09-08 CN CN201780094626.5A patent/CN111278978B/zh active Active
- 2017-09-08 US US16/644,940 patent/US11458172B2/en active Active
-
2018
- 2018-08-14 WO PCT/CN2018/100424 patent/WO2019047679A1/en unknown
- 2018-08-14 JP JP2020513883A patent/JP7102512B2/ja active Active
- 2018-08-14 CN CN201880057532.5A patent/CN111315868B/zh active Active
- 2018-08-14 CN CN202310894227.4A patent/CN116948931A/zh active Pending
- 2018-08-14 EP EP18854715.2A patent/EP3679123A4/en active Pending
- 2018-08-14 US US16/644,942 patent/US11696931B2/en active Active
- 2018-08-14 SG SG11202001796SA patent/SG11202001796SA/en unknown
- 2018-08-14 MY MYPI2020001053A patent/MY200161A/en unknown
-
2022
- 2022-04-28 US US17/661,288 patent/US20220273730A1/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012087483A1 (en) | 2010-11-24 | 2012-06-28 | The Arizona Board Of Regents For And On Behalf Of Arizona State University | Recombinant bacterium comprising a toxin/antitoxin system |
WO2015118541A1 (en) | 2014-02-05 | 2015-08-13 | Gavish-Galilee Bio Applications Ltd | A genetic system for generating conditionally inactivated or attenuated bacteria |
Non-Patent Citations (2)
Title |
---|
Nature Reviews Cancer, 2010, Vol.10, pp.785-794 |
Quantitative Metabolome Profiling of Colon and Stomach Cancer Microenvironment by Capillary Electrophoresis Time-of-Flight Mass Spectrometry,Cancer Research,2009年,Volume 69, Issue 11,pp. 4918-4925 |
Also Published As
Publication number | Publication date |
---|---|
EP3679142A4 (en) | 2021-04-28 |
WO2019047679A1 (en) | 2019-03-14 |
MY200161A (en) | 2023-12-09 |
JP2020532994A (ja) | 2020-11-19 |
CN111315868B (zh) | 2023-08-18 |
CN111278978B (zh) | 2023-08-18 |
AU2017430856A1 (en) | 2020-04-02 |
JP7102512B2 (ja) | 2022-07-19 |
CN111315868A (zh) | 2020-06-19 |
US11696931B2 (en) | 2023-07-11 |
EP3679123A1 (en) | 2020-07-15 |
US20220273730A1 (en) | 2022-09-01 |
US20200323926A1 (en) | 2020-10-15 |
MY195280A (en) | 2023-01-12 |
US11458172B2 (en) | 2022-10-04 |
EP3679142A1 (en) | 2020-07-15 |
JP2020533978A (ja) | 2020-11-26 |
US20210079405A1 (en) | 2021-03-18 |
CN111278978A (zh) | 2020-06-12 |
CN116948931A (zh) | 2023-10-27 |
EP3679123A4 (en) | 2021-08-04 |
WO2019047166A1 (en) | 2019-03-14 |
AU2018328465A1 (en) | 2020-03-19 |
SG11202001796SA (en) | 2020-03-30 |
SG11202001797TA (en) | 2020-03-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7003232B2 (ja) | グルコース依存性の生存率を介して、細菌が固形腫瘍を特異的に標的とすることを可能にする核酸システム | |
Ryan et al. | Bacterial delivery of a novel cytolysin to hypoxic areas of solid tumors | |
Yu et al. | Bioengineered Escherichia coli Nissle 1917 for tumour‐targeting therapy | |
Hoffman | Tumor-seeking Salmonella amino acid auxotrophs | |
JP2023026681A (ja) | 免疫調節ミニ細胞および使用方法 | |
KR101302088B1 (ko) | 5-플루오로우라실 내성균 및 그 제조방법 | |
Fu et al. | Synergistic antitumor efficacy of suicide/ePNP gene and 6-methylpurine 2′-deoxyriboside via Salmonella against murine tumors | |
Fu et al. | Synergistic antitumoral effects of human telomerase reverse transcriptase‐mediated dual‐apoptosis‐related gene vector delivered by orally attenuated Salmonella enterica Serovar Typhimurium in murine tumor models | |
Fu et al. | Suicide gene/prodrug therapy using salmonella‐mediated delivery of Escherichia coli purine nucleoside phosphorylase gene and 6‐methoxypurine 2′‐deoxyriboside in murine mammary carcinoma 4T1 model | |
AU2017430856B2 (en) | Nucleic acid systems that enable bacteria to specifically target solid tumors via glucose-dependent viability | |
AU2018328465B2 (en) | Bacteria for targeting tumors and treating cancer | |
KR101660294B1 (ko) | glmS 기반의 숙주 벡터 시스템 | |
Shahbaz et al. | Current advances in microbial-based cancer therapies | |
WO2022006748A1 (en) | Genetically engineered live bacteria and methods of constructing the same | |
WO2014049604A2 (en) | A novel biomedical device for cancer therapy | |
WO2023131336A1 (zh) | 具有抗肿瘤活性的经修饰的细菌 | |
WO2022094847A1 (zh) | 工程细菌的细胞裂解液及其在肿瘤治疗中的应用 | |
Han et al. | Bifidobacterium as a delivery system of functional genes for cancer therapy | |
KR20210052337A (ko) | 종양 표적화 살모넬라 갈리나룸 균주 및 이의 용도 | |
Westphal | Snapshots on bacterial tumor colonization | |
Nikolova et al. | Pretreatment of Guinea‐pigs with Iron or Desferal Influences the Course of Yersinia enterocolitica Infections | |
Hoffman | Targeting cancer with amino-acid auxotroph Salmonella typhimurium A1-R |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200701 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20210421 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210427 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210726 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210907 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211122 |
|
TRDD | Decision of grant or rejection written | ||
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20211122 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20211214 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20211228 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7003232 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |