WO2023086935A3 - Aptamer-based small ribonucleic acid delivery platform and uses thereof - Google Patents
Aptamer-based small ribonucleic acid delivery platform and uses thereof Download PDFInfo
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- WO2023086935A3 WO2023086935A3 PCT/US2022/079711 US2022079711W WO2023086935A3 WO 2023086935 A3 WO2023086935 A3 WO 2023086935A3 US 2022079711 W US2022079711 W US 2022079711W WO 2023086935 A3 WO2023086935 A3 WO 2023086935A3
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- WO
- WIPO (PCT)
- Prior art keywords
- rna
- aptamer
- oligonucleotides
- delivery platform
- based small
- Prior art date
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- 108091023037 Aptamer Proteins 0.000 title abstract 4
- 229920002477 rna polymer Polymers 0.000 title 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 abstract 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract 4
- 108091034117 Oligonucleotide Proteins 0.000 abstract 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 3
- 210000004027 cell Anatomy 0.000 abstract 3
- 108091008102 DNA aptamers Proteins 0.000 abstract 2
- 108700011259 MicroRNAs Proteins 0.000 abstract 2
- 235000012000 cholesterol Nutrition 0.000 abstract 2
- 239000002679 microRNA Substances 0.000 abstract 2
- 239000002105 nanoparticle Substances 0.000 abstract 2
- 108091032955 Bacterial small RNA Proteins 0.000 abstract 1
- 238000000137 annealing Methods 0.000 abstract 1
- 230000000295 complement effect Effects 0.000 abstract 1
- 210000000172 cytosol Anatomy 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 230000030279 gene silencing Effects 0.000 abstract 1
- 238000012226 gene silencing method Methods 0.000 abstract 1
- 230000002209 hydrophobic effect Effects 0.000 abstract 1
- 230000002132 lysosomal effect Effects 0.000 abstract 1
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- C—CHEMISTRY; METALLURGY
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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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering N.A.
- C12N2310/141—MicroRNAs, miRNAs
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/16—Aptamers
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/321—2'-O-R Modification
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/344—Position-specific modifications, e.g. on every purine, at the 3'-end
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3515—Lipophilic moiety, e.g. cholesterol
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3519—Fusion with another nucleic acid
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- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
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- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
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- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Plant Pathology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Provided herein is a composition comprising an aptamer-based small RNA delivery platform comprising: an aptamer portion comprising a DNA aptamer linked to a first passenger RNA portion; a guide strand RNA of a microRNA (miRNA); and, a second passenger RNA portion conjugated to a cholesterol, wherein the three oligonucleotides assemble through complementary base pair annealing and the hydrophobic cholesterol forms a self-assembled micelle-like nanoparticle with hydrophilic RNA oligonucleotides linked with DNA aptamers on its surface. The aptamer binds to a cell surface molecule for targeted delivery of RNA therapeutics to specific cell surface markers, and once inside the cell, the nanoparticles induce lysosomal leakage, resulting in release of the RNA oligonucleotides into the cytosol, thereby achieving gene silencing.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US202163278868P | 2021-11-12 | 2021-11-12 | |
US63/278,868 | 2021-11-12 |
Publications (2)
Publication Number | Publication Date |
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WO2023086935A2 WO2023086935A2 (en) | 2023-05-19 |
WO2023086935A3 true WO2023086935A3 (en) | 2024-03-28 |
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PCT/US2022/079711 WO2023086935A2 (en) | 2021-11-12 | 2022-11-11 | Aptamer-based small ribonucleic acid delivery platform and uses thereof |
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WO (1) | WO2023086935A2 (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160208245A1 (en) * | 2015-01-21 | 2016-07-21 | Korea Institute Of Science And Technology | RNA/DNA nanoparticle for siRNA target-specific delivery and vehicle including the same |
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2022
- 2022-11-11 WO PCT/US2022/079711 patent/WO2023086935A2/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160208245A1 (en) * | 2015-01-21 | 2016-07-21 | Korea Institute Of Science And Technology | RNA/DNA nanoparticle for siRNA target-specific delivery and vehicle including the same |
Non-Patent Citations (3)
Title |
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BYEONGGEOL MUN,EUNJI JANG, SEUNGMIN HAN, HYE YOUNG SON, YUNA CHOI, YONG-MIN HUH, SEUNGJOO HAAM: "Efficient Self-Assembled MicroRNA Delivery System Consisting of Cholesterol-Conjugated MicroRNA and PEGylated Polycationic Polymer for Tumor Treatment", ACS APPLIED BIO MATERIALS, vol. 2, no. 5, 20 May 2019 (2019-05-20), US , pages 2219 - 2228, XP093155206, ISSN: 2576-6422, DOI: 10.1021/acsabm.9b00186 * |
TOSHIHIKO TANNO: "A novel aptamer-based small RNA delivery platform and its application to cancer therapy", GENES & DISEASES, vol. 10, no. 3, 1 May 2023 (2023-05-01), NL , pages 1075 - 1089, XP093155209, ISSN: 2352-3042, DOI: 10.1016/j.gendis.2022.05.004 * |
Y. WU, K. SEFAH, H. LIU, R. WANG, W. TAN: "DNA aptamer-micelle as an efficient detection/delivery vehicle toward cancer cells", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, vol. 107, no. 1, 5 January 2010 (2010-01-05), pages 5 - 10, XP055423110, ISSN: 0027-8424, DOI: 10.1073/pnas.0909611107 * |
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WO2023086935A2 (en) | 2023-05-19 |
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