ES2673007T1 - Bacterias probióticas recombinantes - Google Patents
Bacterias probióticas recombinantes Download PDFInfo
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- ES2673007T1 ES2673007T1 ES15821025.2T ES15821025T ES2673007T1 ES 2673007 T1 ES2673007 T1 ES 2673007T1 ES 15821025 T ES15821025 T ES 15821025T ES 2673007 T1 ES2673007 T1 ES 2673007T1
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- probiotic bacteria
- factor
- recombinant probiotic
- bacteria according
- recombinant
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- 241000894006 Bacteria Species 0.000 title claims abstract 36
- 239000006041 probiotic Substances 0.000 title claims abstract 35
- 230000000529 probiotic effect Effects 0.000 title claims abstract 35
- 235000018291 probiotics Nutrition 0.000 title claims abstract 35
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract 10
- 150000007523 nucleic acids Chemical group 0.000 claims abstract 10
- 239000003102 growth factor Substances 0.000 claims abstract 8
- 108090000623 proteins and genes Proteins 0.000 claims 9
- 208000027418 Wounds and injury Diseases 0.000 claims 7
- 230000001939 inductive effect Effects 0.000 claims 5
- 201000004624 Dermatitis Diseases 0.000 claims 4
- 230000002757 inflammatory effect Effects 0.000 claims 4
- 239000000203 mixture Substances 0.000 claims 4
- 230000005995 skin dysfunction Effects 0.000 claims 4
- 108010053775 Nisin Proteins 0.000 claims 3
- NVNLLIYOARQCIX-MSHCCFNRSA-N Nisin Chemical compound N1C(=O)[C@@H](CC(C)C)NC(=O)C(=C)NC(=O)[C@@H]([C@H](C)CC)NC(=O)[C@@H](NC(=O)C(=C/C)/NC(=O)[C@H](N)[C@H](C)CC)CSC[C@@H]1C(=O)N[C@@H]1C(=O)N2CCC[C@@H]2C(=O)NCC(=O)N[C@@H](C(=O)N[C@H](CCCCN)C(=O)N[C@@H]2C(NCC(=O)N[C@H](C)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCSC)C(=O)NCC(=O)N[C@H](CS[C@@H]2C)C(=O)N[C@H](CC(N)=O)C(=O)N[C@H](CCSC)C(=O)N[C@H](CCCCN)C(=O)N[C@@H]2C(N[C@H](C)C(=O)N[C@@H]3C(=O)N[C@@H](C(N[C@H](CC=4NC=NC=4)C(=O)N[C@H](CS[C@@H]3C)C(=O)N[C@H](CO)C(=O)N[C@H]([C@H](C)CC)C(=O)N[C@H](CC=3NC=NC=3)C(=O)N[C@H](C(C)C)C(=O)NC(=C)C(=O)N[C@H](CCCCN)C(O)=O)=O)CS[C@@H]2C)=O)=O)CS[C@@H]1C NVNLLIYOARQCIX-MSHCCFNRSA-N 0.000 claims 3
- 239000000411 inducer Substances 0.000 claims 3
- 239000004309 nisin Substances 0.000 claims 3
- 235000010297 nisin Nutrition 0.000 claims 3
- 108010062877 Bacteriocins Proteins 0.000 claims 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims 2
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 claims 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims 2
- 102000003814 Interleukin-10 Human genes 0.000 claims 2
- 108090000174 Interleukin-10 Proteins 0.000 claims 2
- 102100033499 Interleukin-34 Human genes 0.000 claims 2
- 101710181549 Interleukin-34 Proteins 0.000 claims 2
- 102000004388 Interleukin-4 Human genes 0.000 claims 2
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- 241000194036 Lactococcus Species 0.000 claims 2
- 241000194035 Lactococcus lactis Species 0.000 claims 2
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 claims 2
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- 102000013275 Somatomedins Human genes 0.000 claims 2
- 235000014897 Streptococcus lactis Nutrition 0.000 claims 2
- 208000025865 Ulcer Diseases 0.000 claims 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims 2
- 230000009368 gene silencing by RNA Effects 0.000 claims 2
- 229940076144 interleukin-10 Drugs 0.000 claims 2
- 229940028885 interleukin-4 Drugs 0.000 claims 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
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- 108010041525 Alanine racemase Proteins 0.000 claims 1
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- NOQGZXFMHARMLW-UHFFFAOYSA-N Daminozide Chemical compound CN(C)NC(=O)CCC(O)=O NOQGZXFMHARMLW-UHFFFAOYSA-N 0.000 claims 1
- 206010011985 Decubitus ulcer Diseases 0.000 claims 1
- 101100153154 Escherichia phage T5 thy gene Proteins 0.000 claims 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims 1
- 102000018710 Heparin-binding EGF-like Growth Factor Human genes 0.000 claims 1
- 101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 claims 1
- 101100118545 Holotrichia diomphalia EGF-like gene Proteins 0.000 claims 1
- 102000003816 Interleukin-13 Human genes 0.000 claims 1
- 108090000176 Interleukin-13 Proteins 0.000 claims 1
- 241000186660 Lactobacillus Species 0.000 claims 1
- 241000194034 Lactococcus lactis subsp. cremoris Species 0.000 claims 1
- 108700005443 Microbial Genes Proteins 0.000 claims 1
- 201000009053 Neurodermatitis Diseases 0.000 claims 1
- 208000004210 Pressure Ulcer Diseases 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
- 101100313751 Rickettsia conorii (strain ATCC VR-613 / Malish 7) thyX gene Proteins 0.000 claims 1
- 235000014962 Streptococcus cremoris Nutrition 0.000 claims 1
- 108010022394 Threonine synthase Proteins 0.000 claims 1
- 102000005497 Thymidylate Synthase Human genes 0.000 claims 1
- 108010009583 Transforming Growth Factors Proteins 0.000 claims 1
- 102000009618 Transforming Growth Factors Human genes 0.000 claims 1
- 108010075344 Tryptophan synthase Proteins 0.000 claims 1
- 208000000558 Varicose Ulcer Diseases 0.000 claims 1
- 206010052428 Wound Diseases 0.000 claims 1
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- 210000000349 chromosome Anatomy 0.000 claims 1
- 210000002808 connective tissue Anatomy 0.000 claims 1
- 238000012217 deletion Methods 0.000 claims 1
- 230000037430 deletion Effects 0.000 claims 1
- 230000004049 epigenetic modification Effects 0.000 claims 1
- 230000008014 freezing Effects 0.000 claims 1
- 238000007710 freezing Methods 0.000 claims 1
- 229960002897 heparin Drugs 0.000 claims 1
- 229920000669 heparin Polymers 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 230000000302 ischemic effect Effects 0.000 claims 1
- 235000014655 lactic acid Nutrition 0.000 claims 1
- 239000004310 lactic acid Substances 0.000 claims 1
- 229940039696 lactobacillus Drugs 0.000 claims 1
- 206010025135 lupus erythematosus Diseases 0.000 claims 1
- 230000035772 mutation Effects 0.000 claims 1
- 108010074461 nisin A Proteins 0.000 claims 1
- 108700042622 nisin Z Proteins 0.000 claims 1
- 239000013612 plasmid Substances 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 101150054232 pyrG gene Proteins 0.000 claims 1
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- 239000000243 solution Substances 0.000 claims 1
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- 239000007921 spray Substances 0.000 claims 1
- 238000010254 subcutaneous injection Methods 0.000 claims 1
- 239000007929 subcutaneous injection Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 101150072314 thyA gene Proteins 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
- C12N15/746—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for lactic acid bacteria (Streptococcus; Lactococcus; Lactobacillus; Pediococcus; Enterococcus; Leuconostoc; Propionibacterium; Bifidobacterium; Sporolactobacillus)
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Abstract
Bacterias probióticas recombinantes, que comprenden (a) secuencia o secuencias de ácido nucleico que codifican un primer factor heterólogo, (a) secuencia o secuencias de ácido nucleico que codifican un segundo factor heterólogo y preferiblemente (a) secuencia o secuencias de ácido nucleico que codifican un tercer factor heterólogo, con la condición de que dicho primer factor, dicho segundo factor y dicho tercer factor son funcionalmente diferentes entre sí, en las que dicho primer factor es un factor de crecimiento, en las que dicho segundo factor se selecciona del grupo que consiste en factores polarizantes de M2, y en las que preferiblemente dicho tercer factor se selecciona del grupo que consiste en factores polarizantes de M2 y factores de crecimiento.
Claims (23)
- REIVINDICACIONES1. Bacterias probióticas recombinantes, que comprenden(a) secuencia o secuencias de ácido nucleico que codifican un primer factor heterólogo, (a) secuencia o secuencias de ácido nucleico que codifican un segundo factor heterólogo y preferiblemente (a) secuencia o secuencias de ácido nucleico que codifican un tercer factor heterólogo, con la condición de que dicho primer factor, dicho segundo factor y dicho tercer factor son funcionalmente diferentes entre sí,en las que dicho primer factor es un factor de crecimiento, en las que dicho segundo factor se selecciona del grupo que consiste en factores polarizantes de M2, y en las que preferiblemente dicho tercer factor se selecciona del grupo que consiste en factores polarizantes de M2 y factores de crecimiento.
- 2. Bacterias probióticas recombinantes, según la reivindicación 1, en las que dicha secuencia o secuencias de ácido nucleico están situadas en al menos uno de un cromosoma y un plásmido de dichas bacterias probióticas recombinantes.
- 3. Bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 1 ó 2, en las que la expresión de dicha secuencia o secuencias de ácido nucleico está controlada por un promotor constitutivo o un promotor inducible.
- 4. Bacterias probióticas recombinantes, según la reivindicación 3, en las que la expresión de dicha secuencia o secuencias de ácido nucleico está controlada por un promotor inducible, siendo dicha secuencia o secuencias de ácido nucleico expresables en presencia de al menos un inductor.
- 5. Bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 3 ó 4, en las que dicho promotor inducible, que es inducible por un inductor, es un promotor para un gen microbiano que codifica un péptido lantibiótico o un análogo funcional del mismo, en las que preferiblemente dicho promotor inducible es PnisA, PnisZ, PnisQ, PnisF, PnisU o combinaciones de los mismos de Lactococcus lactis.
- 6. Bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 4 o 5, en las que el inductor es al menos un péptido lantibiótico o un análogo funcional del mismo, preferiblemente seleccionado del grupo que consiste en nisina A, nisina Z, nisina Q, nisina F, nisina U, análogos funcionales de las mismas, y mezclas de las mismas.
- 7. Bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 1 a 6, en las que dichas bacterias probióticas comprenden, además, al menos un gen inactivado que codifica una proteína esencial necesaria para la viabilidad de dichas bacterias probióticas.
- 8. Bacterias probióticas recombinantes, según la reivindicación 7, en las que dicho al menos un gen inactivado necesario para la viabilidad de dichas bacterias probióticas se selecciona del grupo que consiste en alanina racemasa (alaR), timidilato sintasa (thyA), asparagina sintasa (asnH), CTP sintasa (pyrG), triptófano sintasa (trpBA), y combinaciones de los mismos.
- 9. Bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 7 u 8, en las que dicho gen se inactiva por deleción de dicho gen, mutación de dicho gen, modificación epigenética de dicho gen, silenciamiento génico mediado por ARN de interferencia (ARNi) de dicho gen, inhibición de la traducción de dicho gen, o combinaciones de los mismos.
- 10. Bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 1 a 9, en las que al menos uno de dicho primer factor, dicho segundo factor y dicho tercer factor es liberable de dichas bacterias probióticas recombinantes.
- 11. Bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 1 a 10, en las que dicho factor polarizante de M2 se selecciona del grupo que consiste en citocinas, quimiocinas y mezclas de las mismas.
- 12. Bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 1 a 11, en las que dicho factor polarizante de M2 se selecciona del grupo que consiste en interleucina 4 (IL-4), interleucina 10 (IL-10), interleucina 13 (IL-13), factor 1 estimulante de colonias (CSF-1), interleucina 34 (IL34) y mezclas de los mismos.
- 13. Bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 1 a 12, en las que dicho factor de crecimiento se selecciona del grupo que consiste en factores de crecimiento de fibroblastos (FGF), factores de crecimiento endotelial vascular (VEGF), factores de crecimiento epidérmico (EGF), factor de crecimiento similar a EGF (HB-EGF) de unión a heparina, factor de crecimiento transformante a (TGF-a), factores de crecimiento similares a la insulina (IGF), factores de crecimiento derivados de plaquetas (PDGF), factor beta de crecimiento transformante (TGF-p) y mezclas de los mismos, preferiblemente el factor 2 de crecimiento de fibroblastos (FGF-2).
- 14. Bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 1 a 13, en las que dichas bacterias probióticas recombinantes son bacterias de ácido láctico, preferiblemente una especie de Lactobacillus o Lactococcus.
- 15. Bacterias probióticas recombinantes, según la reivindicación 14, en las que dicha especie de Lactococcus es Lactococcus lactis, preferiblemente la subespecie cremoris de Lactococcus lactis.
- 16. Bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 1 a 15, en las que dichas bacterias probióticas recombinantes están en una solución, congeladas o secas, preferiblemente están liofilizadas o secadas por pulverización.
- 17. Bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 1 a 16, en las que dichas bacterias probióticas recombinantes se administran por vía tópica y/o mediante inyección subcutánea.
- 18. Bacterias probióticas recombinantes para usar en el tratamiento de una disfunción inflamatoria de la piel, en las que dichas bacterias probióticas recombinantes son bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 1 a 17.
- 19. Bacterias probióticas recombinantes, según la reivindicación 18, en las que dicha disfunción inflamatoria de la piel es una enfermedad inflamatoria de la piel o una enfermedad inflamatoria del tejido conectivo.
- 20. Bacterias probióticas recombinantes, según la reivindicación 19, en las que dicha enfermedad inflamatoria de la piel es la congelación, eczema, psoriasis, dermatitis, úlcera, herida, lupus eritematoso, neurodermitis o combinaciones de las mismas.
- 21. Bacterias probióticas recombinantes, según la reivindicación 20, en las que dicha herida es una herida por quemadura, una herida química, una herida inducida por radiación, una herida isquémica o una herida mecánica.
- 22. Bacterias probióticas recombinantes, según la reivindicación 20, en las que dicha úlcera es una úlcera de decúbito o una úlcera venosa.
- 23. Método para el tratamiento de una disfunción inflamatoria de la piel, en el que dicho método comprende la etapa de administrar bacterias probióticas recombinantes, según cualquiera de las reivindicaciones 1 a 22, a un individuo que padece dicha disfunción inflamatoria de la piel.
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| PCT/EP2015/075484 WO2016124266A1 (en) | 2015-02-04 | 2015-11-02 | Recombinant probiotic bacteria |
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| EP3237622B1 (en) | 2014-12-23 | 2021-02-24 | Ilya Pharma AB | Methods for wound healing |
| EP3512872A1 (en) * | 2016-09-13 | 2019-07-24 | Intrexon Actobiotics NV | Mucoadhesive microorganism |
| US12121573B2 (en) | 2019-07-14 | 2024-10-22 | Tianxin Wang | Methods and agents including STING agonist to treat tumor |
| WO2019113023A1 (en) * | 2017-12-04 | 2019-06-13 | The BioCollective, LLC | Probiotics and methods of use |
| ES3040400T3 (en) | 2018-02-24 | 2025-10-30 | Clearskin Ltd | Compositions, devices, systems, kits and methods for the treatment of a skin condition |
| KR102283127B1 (ko) * | 2018-06-19 | 2021-07-29 | 주식회사 엠디헬스케어 | 류코노스톡속 균주를 포함하는 간 기능 개선용 조성물 |
| EP3837993A4 (en) * | 2018-06-19 | 2022-04-20 | Coenbio Co., Ltd. | Composition for improving intestinal function comprising leuconostoc sp. strain |
| KR102173168B1 (ko) * | 2018-06-19 | 2020-11-03 | 주식회사 엠디헬스케어 | 류코노스톡속 균주를 포함하는 장 기능 개선용 조성물 |
| EP3837992A4 (en) * | 2018-06-19 | 2022-03-30 | Coenbio Co., Ltd. | COMPOSITION COMPRISING A STRAIN OF LEUCONOSTOC SP. TO IMPROVE HEPATIC FUNCTION |
| US20220177533A1 (en) * | 2018-08-08 | 2022-06-09 | Sree Chitra Tirunal Institute For Medical Sciences And Technology | Recombinant TGF a for wound healing purposes, and the process thereof |
| CN109078171A (zh) * | 2018-09-10 | 2018-12-25 | 因之彩生物科技（武汉）有限公司 | 一种外用组合物及其应用以及外用治疗剂 |
| IT201900003115A1 (it) * | 2019-03-04 | 2020-09-04 | Univ Degli Studi Roma La Sapienza | Lattococco ingegnerizzato |
| AU2019433065B2 (en) * | 2019-03-04 | 2022-08-18 | Aurealis Therapeutics AG | Chloride-inducible prokaryotic expression system |
| BR112021023682A2 (pt) | 2019-06-24 | 2022-04-12 | Mendes Srl | Composição com ação antibacteriana e de reepitelização incluindo probióticos |
| CN112175890A (zh) * | 2019-07-02 | 2021-01-05 | 深伦生物科技（深圳）有限公司 | 一种以食用菌分泌乙醇脱氢酶的基因工程菌 |
| KR102343938B1 (ko) * | 2020-09-02 | 2021-12-28 | 주식회사 비피도 | 재조합 비피도박테리움 비피덤 bgn4를 포함하는 염증 개선용 조성물 |
| CN112359049B (zh) * | 2020-12-10 | 2022-01-28 | 昆明理工大学 | 一种岷江百合几丁质酶基因LrCHI2及其应用 |
| KR102253283B1 (ko) * | 2020-12-21 | 2021-05-18 | 주식회사 비피도 | 비피도박테리움 비피덤을 이용한 인간 egf 단백질의 생산방법 및 이를 함유하는 조성물 |
| WO2022187724A1 (en) * | 2021-03-05 | 2022-09-09 | The Regents Of The University Of California | Skin probiotics |
| KR102809763B1 (ko) * | 2021-12-06 | 2025-05-20 | 주식회사 바이오에프디엔씨 | 세포 투과형 성장인자를 포함하는 세포 배양 또는 증식을 위한 조성물 |
| CN114395514B (zh) * | 2022-02-28 | 2023-09-01 | 鲁东大学 | 一株嗜酸乳杆菌、菌剂及其应用 |
| KR102838081B1 (ko) * | 2022-04-12 | 2025-07-24 | 고려대학교 산학협력단 | 마이크로바이옴을 이용하여 당뇨족부궤양 예후를 예측하는 방법 |
| CN114957437B (zh) * | 2022-06-06 | 2023-03-21 | 陕西理工大学 | 一种leap-2重组蛋白和一种重组乳酸乳球菌及其应用 |
| CN115181710B (zh) * | 2022-09-13 | 2022-11-25 | 北京量化健康科技有限公司 | 一株唾液乳杆菌b12wu及其应用 |
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| EP2963012B1 (en) | 2008-11-11 | 2018-01-10 | Signum Biosciences, Inc. | Isoprenyl compounds and methods thereof |
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| US20130078275A1 (en) * | 2010-05-25 | 2013-03-28 | The Board Of Trustees Of The University Of Illinois | Novel systems, vectors, and methods for delivery of biomolecules to eukaryotic cells |
| CN107325979B (zh) * | 2010-06-18 | 2023-01-24 | 北卡罗莱纳州立大学 | 减少炎性反应的具有减少的脂磷壁酸的重组乳杆菌 |
| CN101892189B (zh) | 2010-07-05 | 2012-07-04 | 浙江大学 | 一种口服免疫阻断猪生长抑素作用的转化子及其应用 |
| JP2012019768A (ja) * | 2010-07-16 | 2012-02-02 | Osaka Univ | Ｊｍｊｄ３遺伝子改変非ヒト哺乳動物、Ｊｍｊｄ３遺伝子改変骨髄キメラ非ヒト哺乳動物、及びその利用 |
| TWI566701B (zh) | 2012-02-01 | 2017-01-21 | 日本農藥股份有限公司 | 芳烷氧基嘧啶衍生物及包含該衍生物作為有效成分的農園藝用殺蟲劑及其使用方法 |
| GB201206599D0 (en) * | 2012-04-13 | 2012-05-30 | Univ Manchester | Probiotic bacteria |
| TWI613833B (zh) | 2012-11-09 | 2018-02-01 | Sony Corp | 光電變換元件、固體攝像裝置及電子機器 |
| JP2016503422A (ja) * | 2012-11-16 | 2016-02-04 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | プロスタグランジンｅｐ４アゴニストの組み合わせを用いた皮膚創傷の治癒および瘢痕の減少 |
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- 2015-11-02 CN CN201580078514.1A patent/CN107438666B/zh active Active
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