WO2018170766A1 - Arnsi du gène humain codant pour le ligand de mort cellulaire programmée 2 et son application - Google Patents
Arnsi du gène humain codant pour le ligand de mort cellulaire programmée 2 et son application Download PDFInfo
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- WO2018170766A1 WO2018170766A1 PCT/CN2017/077608 CN2017077608W WO2018170766A1 WO 2018170766 A1 WO2018170766 A1 WO 2018170766A1 CN 2017077608 W CN2017077608 W CN 2017077608W WO 2018170766 A1 WO2018170766 A1 WO 2018170766A1
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- WO
- WIPO (PCT)
- Prior art keywords
- gene
- sirna
- application
- seq
- programmed death
- Prior art date
Links
- 108020004459 Small interfering RNA Proteins 0.000 title abstract description 12
- 101001117312 Homo sapiens Programmed cell death 1 ligand 2 Proteins 0.000 title description 6
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 claims abstract description 20
- 230000014509 gene expression Effects 0.000 claims abstract description 13
- 230000000692 anti-sense effect Effects 0.000 claims abstract description 4
- 239000003814 drug Substances 0.000 claims abstract description 4
- 108091081021 Sense strand Proteins 0.000 claims abstract description 3
- 201000010099 disease Diseases 0.000 claims abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 3
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 claims abstract 3
- 230000002159 abnormal effect Effects 0.000 claims abstract 2
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 claims description 6
- 230000009368 gene silencing by RNA Effects 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
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000012634 fragment Substances 0.000 claims 3
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 abstract description 13
- 108020004999 messenger RNA Proteins 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 12
- 239000004055 small Interfering RNA Substances 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 238000003753 real-time PCR Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 230000000139 costimulatory effect Effects 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 238000002123 RNA extraction Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 102000048119 human PDCD1LG2 Human genes 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
Definitions
- the present invention belongs to the field of molecular genetics, and more particularly to a siRN capable of inhibiting human programmed death ligand 2
- Non-small cell lung cancer is a common malignant tumor in the world, and its incidence is increasing year by year. Studying NSCLC tumor recurrence factors and tumor immune escape mechanisms has important theoretical significance and clinical application value. T lymphocytes are important effector cells that mediate tumor immune responses, and T cell activation requires TCR-mediated antigen-specific signaling and costimulatory molecule-mediated costimulatory signals.
- PD-L2 Programmed death ligand 2
- B7-H1 is a negative T cell costimulatory molecule in the B7 family
- PD-L2 inhibits proliferation of CD4 and CD8 T cells by binding to its receptor PD-1
- activation negative regulation of the body's immune response process, thereby mediating tumor immune escape, promoting tumor growth
- the role of PD-L2 in tumor escape has an important role in the prevention and treatment of tumors, but the lack of specificity in the prior art
- the vector that inhibits the expression of the PD-L2 gene makes the related research not well developed.
- RNAi small interfering RNA
- siPDL2 sequence is as follows: [0007] Justice strand: 5,- GAGGGAAGUGAACAGUGCU-3' (SEQ ID NO: l);
- Antisense strand 5,-AGCACUGUUCACUUCCCUC-3' (SEQ ID NO: 2).
- 1 is a schematic diagram showing the results of quantitative PCR detection of PD-L2 gene expression levels after HepG2 cells transfected with siPDL2.
- Total RNA extraction Total RNA of PD-L2 cells normal and transfected with siPDL2 was extracted using the QIAGEN RNeasy Mini Kit.
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention concerne un ARNsi capable d'inhiber de manière efficace et spécifique l'expression, au niveau ARNm, d'un gène PD-L2, les séquences de celui-ci étant les suivantes : brin sens : 5'-GAGGGAAGUGAACAGUGCU-3'(SEQ ID NO:1) ; et brin antisens : 5'-AGCACUGUUCACUUCCCUC-3'(SEQ ID NO:2). L'invention concerne également une application de cet ARNsi dans la préparation de médicaments destinés au traitement de maladies associées à une expression anormale du gène PD-L2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2017/077608 WO2018170766A1 (fr) | 2017-03-22 | 2017-03-22 | Arnsi du gène humain codant pour le ligand de mort cellulaire programmée 2 et son application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2017/077608 WO2018170766A1 (fr) | 2017-03-22 | 2017-03-22 | Arnsi du gène humain codant pour le ligand de mort cellulaire programmée 2 et son application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2018170766A1 true WO2018170766A1 (fr) | 2018-09-27 |
Family
ID=63584900
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2017/077608 WO2018170766A1 (fr) | 2017-03-22 | 2017-03-22 | Arnsi du gène humain codant pour le ligand de mort cellulaire programmée 2 et son application |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2018170766A1 (fr) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102428179A (zh) * | 2009-03-06 | 2012-04-25 | 国立大学法人三重大学 | 用于增强t细胞功能的方法 |
-
2017
- 2017-03-22 WO PCT/CN2017/077608 patent/WO2018170766A1/fr active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102428179A (zh) * | 2009-03-06 | 2012-04-25 | 国立大学法人三重大学 | 用于增强t细胞功能的方法 |
Non-Patent Citations (4)
| Title |
|---|
| HOBO, W. ET AL.: "siRNA silencing of PD - LI and PD - L2 on dendritic cells augments expansion and function of minor histocompatibility antigen-specific CD 8+ T cells", BLOOD, vol. 116, no. 22, 25 November 2010 (2010-11-25), pages 4501 - 4511, XP055298201, ISSN: 0006-4971 * |
| ROZALI, E. N. ET AL.: "Programmed Death Ligand 2 in Cancer-Induced Immune Suppression", CLINICAL AND DEVELOPMENTAL IMMUNOLOGY, vol. 2012, 31 December 2012 (2012-12-31), pages 1 - 9, XP055539612, ISSN: 1740-2522 * |
| WANG, GUOYAN ET AL.: "PD-L1/PD-L2 on Human Placenta-Derived Mesenchymal Stem Cells Inhibits the IL 17 Secretion of Peripheral Blood T Cells", CHINESE JOURNAL OF CELLULAR AND MOLECULAR IMMUNOLOGY, vol. 29, no. 2, 31 December 2013 (2013-12-31), pages 132 - 136, ISSN: 1007-8738 * |
| ZHANG, SIYING ET AL.: "PD -Between L2 in Human Placenta Mesenchymal Stem Cells on the Expression and Its Biological Significance", JOURNAL OF HEZE MEDICAL COLLEGE, 31 December 2013 (2013-12-31), ISSN: 1008-4118 * |
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