CA2590768A1 - Rnai modulation of mll-af4 and uses thereof - Google Patents
Rnai modulation of mll-af4 and uses thereof Download PDFInfo
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- CA2590768A1 CA2590768A1 CA002590768A CA2590768A CA2590768A1 CA 2590768 A1 CA2590768 A1 CA 2590768A1 CA 002590768 A CA002590768 A CA 002590768A CA 2590768 A CA2590768 A CA 2590768A CA 2590768 A1 CA2590768 A1 CA 2590768A1
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- irna agent
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Classifications
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- 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
- C12N15/113—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
- C12N15/1135—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 against oncogenes or tumor suppressor genes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
Landscapes
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- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
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- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
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- Zoology (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
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- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Inductance-Capacitance Distribution Constants And Capacitance-Resistance Oscillators (AREA)
- Oscillators With Electromechanical Resonators (AREA)
- Control Of El Displays (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63593604P | 2004-12-14 | 2004-12-14 | |
| US60/635,936 | 2004-12-14 | ||
| US66839205P | 2005-04-05 | 2005-04-05 | |
| US60/668,392 | 2005-04-05 | ||
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Families Citing this family (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007001448A2 (en) | 2004-11-04 | 2007-01-04 | Massachusetts Institute Of Technology | Coated controlled release polymer particles as efficient oral delivery vehicles for biopharmaceuticals |
| EP1824872B1 (en) * | 2004-12-14 | 2012-02-08 | Alnylam Pharmaceuticals Inc. | Rnai modulation of mll-af4 and uses thereof |
| WO2007016548A2 (en) * | 2005-08-01 | 2007-02-08 | The Ohio State University Research Foundation | Micro-rna-based methods and compositions for the diagnosis, prognosis and treatment of breast cancer |
| US8481505B2 (en) * | 2005-09-12 | 2013-07-09 | The Ohio State University Research Foundation | Compositions and methods for the diagnosis and therapy of BCL2-associated cancers |
| CA2624531A1 (en) * | 2005-10-05 | 2007-04-19 | Carlo M. Croce | Wwox gene, vectors containing the same, and uses in treatment of cancer |
| US9267937B2 (en) | 2005-12-15 | 2016-02-23 | Massachusetts Institute Of Technology | System for screening particles |
| AU2007205234B2 (en) | 2006-01-05 | 2012-07-12 | The Ohio State University Research Foundation | MicroRNA-based methods and compositions for the diagnosis, prognosis and treatment of lung cancer |
| WO2007081680A2 (en) | 2006-01-05 | 2007-07-19 | The Ohio State University Research Foundation | Microrna expression abnormalities in pancreatic endocrine and acinar tumors |
| EP2484782B1 (en) | 2006-01-05 | 2015-11-18 | The Ohio State University Research Foundation | MicroRNA-based methods and compositions for the diagnosis and treatment of solid cancers |
| ES2446362T3 (es) | 2006-03-20 | 2014-03-07 | The Ohio State University Research Foundation | Huellas de microARN durante megacariocipoyesis humana |
| US8367113B2 (en) | 2006-05-15 | 2013-02-05 | Massachusetts Institute Of Technology | Polymers for functional particles |
| WO2007150030A2 (en) | 2006-06-23 | 2007-12-27 | Massachusetts Institute Of Technology | Microfluidic synthesis of organic nanoparticles |
| ES2425387T3 (es) | 2006-07-13 | 2013-10-15 | The Ohio State University Research Foundation | Mir-106a para diagnosticar adenocarcinoma de colon de pronóstico de supervivencia pobre |
| US8071292B2 (en) | 2006-09-19 | 2011-12-06 | The Ohio State University Research Foundation | Leukemia diagnostic methods |
| WO2008054828A2 (en) | 2006-11-01 | 2008-05-08 | The Ohio State University Research Foundation | Microrna expression signature for predicting survival and metastases in hepatocellular carcinoma |
| JP2010516291A (ja) * | 2007-01-31 | 2010-05-20 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイション | 急性骨髄性白血病（ａｍｌ）の診断、予後及び治療のためのマイクロｒｎａに基づく方法及び組成物 |
| US9217129B2 (en) | 2007-02-09 | 2015-12-22 | Massachusetts Institute Of Technology | Oscillating cell culture bioreactor |
| US20090074828A1 (en) | 2007-04-04 | 2009-03-19 | Massachusetts Institute Of Technology | Poly(amino acid) targeting moieties |
| CN101827941B (zh) * | 2007-04-30 | 2014-07-16 | 俄亥俄州立大学研究基金会 | 用于区分胰腺癌与正常胰腺功能和/或慢性胰腺炎的方法 |
| US8465917B2 (en) * | 2007-06-08 | 2013-06-18 | The Ohio State University Research Foundation | Methods for determining heptocellular carcinoma subtype and detecting hepatic cancer stem cells |
| US8053186B2 (en) | 2007-06-15 | 2011-11-08 | The Ohio State University Research Foundation | Oncogenic ALL-1 fusion proteins for targeting Drosha-mediated microRNA processing |
| AR066984A1 (es) * | 2007-06-15 | 2009-09-23 | Novartis Ag | Inhibicion de la expresion de la subunidad alfa del canal epitelial de sodio (enac) por medio de arni (arn de interferencia) |
| EP2173911B1 (en) * | 2007-07-31 | 2014-06-18 | The Ohio State University Research Foundation | Methods for reverting methylation by targeting dnmt3a and dnmt3b |
| EP2653561B1 (en) * | 2007-08-03 | 2016-03-02 | The Ohio State University Research Foundation | Ultraconserved regions encoding ncRNAs |
| EP3028708A1 (en) * | 2007-08-22 | 2016-06-08 | The Ohio State University Research Foundation | Methods and compositions for inducing deregulation of epha7 and erk phosphorylation in human acute leukemias |
| TW200918099A (en) | 2007-09-14 | 2009-05-01 | Nitto Denko Corp | Drug carriers |
| ATE530169T1 (de) | 2007-09-28 | 2011-11-15 | Bind Biosciences Inc | Krebszellen-targeting mit nanopartikeln |
| MX2010003642A (es) | 2007-10-12 | 2010-08-09 | Massachusetts Inst Technology | Nanotecnologia de vacuna. |
| WO2009055773A2 (en) | 2007-10-26 | 2009-04-30 | The Ohio State University Research Foundation | Methods for identifying fragile histidine triad (fhit) interaction and uses thereof |
| EP2225396A4 (en) * | 2007-11-30 | 2011-03-02 | Univ Ohio State Res Found | PROFILING AND SCREENING OF MICRO-RNA EXPRESSION IN PERIPHERAL BLOOD IN LUNG CANCER |
| US8188060B2 (en) | 2008-02-11 | 2012-05-29 | Dharmacon, Inc. | Duplex oligonucleotides with enhanced functionality in gene regulation |
| JP2011517932A (ja) * | 2008-02-28 | 2011-06-23 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイション | ヒト慢性リンパ球性白血病（ｃｃｌ）と関連するマイクロｒｎａシグネチャーおよびその使用 |
| US20110054009A1 (en) * | 2008-02-28 | 2011-03-03 | The Ohio State University Research Foundation | MicroRNA-Based Methods and Compositions for the Diagnosis, Prognosis and Treatment of Prostate Related Disorders |
| WO2009152300A1 (en) | 2008-06-11 | 2009-12-17 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Use of mir-26 family as a predictive marker of hepatocellular carcinoma and responsiveness to therapy |
| EP2329023B1 (en) * | 2008-08-28 | 2016-07-27 | Council of Scientific & Industrial Research | Compositions and methods for delivery of protein-coding rnas to correct mitochondrial dysfunction |
| US8277812B2 (en) | 2008-10-12 | 2012-10-02 | Massachusetts Institute Of Technology | Immunonanotherapeutics that provide IgG humoral response without T-cell antigen |
| US8591905B2 (en) | 2008-10-12 | 2013-11-26 | The Brigham And Women's Hospital, Inc. | Nicotine immunonanotherapeutics |
| US8343498B2 (en) | 2008-10-12 | 2013-01-01 | Massachusetts Institute Of Technology | Adjuvant incorporation in immunonanotherapeutics |
| US8343497B2 (en) | 2008-10-12 | 2013-01-01 | The Brigham And Women's Hospital, Inc. | Targeting of antigen presenting cells with immunonanotherapeutics |
| WO2010138193A2 (en) | 2009-05-27 | 2010-12-02 | Selecta Biosciences, Inc. | Targeted synthetic nanocarriers with ph sensitive release of immunomodulatory agents |
| WO2010141511A2 (en) | 2009-06-01 | 2010-12-09 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotides for multivalent rna interference, compositions and methods of use thereof |
| US8758323B2 (en) | 2009-07-30 | 2014-06-24 | Tandem Diabetes Care, Inc. | Infusion pump system with disposable cartridge having pressure venting and pressure feedback |
| EP2504452A4 (en) | 2009-11-23 | 2014-06-11 | Univ Ohio State Res Found | MATERIALS AND METHODS FOR INFLUENCING GROWTH, MIGRATION AND INVASION OF TUMOR CELLS |
| US8349308B2 (en) | 2010-03-26 | 2013-01-08 | Mersana Therapeutics, Inc. | Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof |
| CN107029223A (zh) | 2010-05-26 | 2017-08-11 | 西莱克塔生物科技公司 | 合成纳米载体联合疫苗 |
| WO2012065049A1 (en) | 2010-11-12 | 2012-05-18 | The Ohio State University Research Foundation | Materials and methods related to microrna-21, mismatch repair, and colorectal cancer |
| CA2817982C (en) | 2010-11-15 | 2020-06-30 | The Regents Of The University Of Michigan | Controlled release mucoadhesive systems |
| WO2012082894A1 (en) * | 2010-12-17 | 2012-06-21 | Arrowhead Research Corporation | Compositions and methods for inhibiting expression of mll genes |
| JP2014509852A (ja) | 2011-03-07 | 2014-04-24 | ジ・オハイオ・ステート・ユニバーシティ | マイクロＲＮＡ−１５５（ｍｉＲ−１５５）により誘導される変異誘発活性は炎症および癌を結び付ける |
| JP2014521687A (ja) | 2011-07-29 | 2014-08-28 | セレクタ バイオサイエンシーズ インコーポレーテッド | 体液性および細胞傷害性ｔリンパ球（ｃｔｌ）免疫応答を生成する合成ナノキャリア |
| CA2852066A1 (en) | 2011-10-14 | 2013-04-18 | The Ohio State University | Methods and materials related to ovarian cancer |
| EP2790735A4 (en) | 2011-12-13 | 2015-12-09 | Ohio State Innovation Foundation | METHODS AND COMPOSITIONS RELATING TO MIR-21 AND MIR-29A, EXOSOME INHIBITION, AND CANCER METASTASIS |
| JP2015511121A (ja) | 2012-01-20 | 2015-04-16 | ジ・オハイオ・ステート・ユニバーシティ | 浸潤性および予後に関する乳がんバイオマーカーシグネチャー |
| US9180242B2 (en) | 2012-05-17 | 2015-11-10 | Tandem Diabetes Care, Inc. | Methods and devices for multiple fluid transfer |
| US9173998B2 (en) | 2013-03-14 | 2015-11-03 | Tandem Diabetes Care, Inc. | System and method for detecting occlusions in an infusion pump |
| MX2018002090A (es) | 2015-08-24 | 2018-09-12 | Halo Bio Rnai Therapeutics Inc | Nanoparticulas de polinucleótido para modulación de expresión génica y sus usos. |
| TN2019000308A1 (en) | 2017-07-06 | 2021-05-07 | Arrowhead Pharmaceuticals Inc | RNAi AGENTS FOR INHIBITING EXPRESSION OF ALPHA-ENaC AND METHODS OF USE |
| CN107964536B (zh) * | 2018-01-19 | 2021-10-22 | 上海交通大学医学院附属瑞金医院 | 一种实现人的诱导多能干细胞来源的造血干祖细胞强效体内移植的方法 |
| MX2024003887A (es) | 2021-10-14 | 2024-07-09 | Arsenal Biosciences Inc | Células inmunitarias que tienen arnch coespresados y sistemas de compuerta lógica. |
| CR20250095A (es) | 2022-09-13 | 2025-09-01 | Arsenal Biosciences Inc | Células inmunitarias que coexpresan arnhc de tgfbr |
| JP2025532585A (ja) | 2022-09-16 | 2025-10-01 | アーセナル バイオサイエンシズ インコーポレイテッド | 組み合わせ遺伝子摂動を有する免疫細胞 |
| TW202442689A (zh) | 2023-03-03 | 2024-11-01 | 美商亞森諾生物科學公司 | 靶向ｐｓｍａ及ｃａ９之系統 |
| TW202544044A (zh) | 2024-03-20 | 2025-11-16 | 美商亞森諾生物科學公司 | 靶向ｓｌｃ３４ａ２及ｔｍｐｒｓｓ４之系統及其使用方法 |
| WO2026136848A2 (en) | 2024-12-20 | 2026-06-25 | Juno Therapeutics, Inc. | Cd70-targeted cars and engineered cells comprising same and related methods |
| WO2026151965A1 (en) | 2025-01-10 | 2026-07-16 | Arsenal Biosciences, Inc. | Shrna targeting fas and tgfbrii genes |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4957735A (en) * | 1984-06-12 | 1990-09-18 | The University Of Tennessee Research Corporation | Target-sensitive immunoliposomes- preparation and characterization |
| US5043164A (en) * | 1989-01-17 | 1991-08-27 | The University Of Tennessee Research Corporation | Blood-stable, cholesterol-free liposomes |
| US5013556A (en) * | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5705187A (en) * | 1989-12-22 | 1998-01-06 | Imarx Pharmaceutical Corp. | Compositions of lipids and stabilizing materials |
| JP3351476B2 (ja) * | 1993-01-22 | 2002-11-25 | 三菱化学株式会社 | リン脂質誘導体及びそれを含有するリポソーム |
| US5853755A (en) * | 1993-07-28 | 1998-12-29 | Pharmaderm Laboratories Ltd. | Biphasic multilamellar lipid vesicles |
| US5820873A (en) * | 1994-09-30 | 1998-10-13 | The University Of British Columbia | Polyethylene glycol modified ceramide lipids and liposome uses thereof |
| US5817856A (en) * | 1995-12-11 | 1998-10-06 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Radiation-protective phospholipid and method |
| US5898031A (en) * | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
| US7045292B2 (en) * | 1998-03-25 | 2006-05-16 | University Of Manitoba | Method and marker for identification of pre-malignancy and malignancy and therapeutic intervention |
| JP2003526367A (ja) * | 2000-03-16 | 2003-09-09 | ジェネティカ インコーポレイテッド | Ｒｎａ干渉の方法とｒｎａ干渉組成物 |
| CN100523215C (zh) * | 2000-12-01 | 2009-08-05 | 马普科技促进协会 | 介导rna干涉的小rna分子 |
| EP1386004A4 (en) * | 2001-04-05 | 2005-02-16 | Ribozyme Pharm Inc | MODULATION OF GENE EXPRESSION ASSOCIATED WITH INFLAMMATORY PROLIFERATION AND GROWTH OF NEURITIES BY METHODS INVOLVING NUCLEIC ACID |
| US20030175950A1 (en) * | 2001-05-29 | 2003-09-18 | Mcswiggen James A. | RNA interference mediated inhibition of HIV gene expression using short interfering RNA |
| US7923547B2 (en) * | 2002-09-05 | 2011-04-12 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
| EP2305813A3 (en) * | 2002-11-14 | 2012-03-28 | Dharmacon, Inc. | Fuctional and hyperfunctional sirna |
| WO2004064737A2 (en) | 2003-01-17 | 2004-08-05 | Alnylam Pharmaceuticals | Therapeutics compositions |
| CA2518475C (en) | 2003-03-07 | 2014-12-23 | Alnylam Pharmaceuticals, Inc. | Irna agents comprising asymmetrical modifications |
| CA2522349A1 (en) | 2003-04-17 | 2004-11-04 | Alnylam Pharmaceuticals, Inc. | Protected monomers |
| EP2669377A3 (en) * | 2003-04-17 | 2015-10-14 | Alnylam Pharmaceuticals Inc. | Modified iRNA agents |
| EP1824872B1 (en) * | 2004-12-14 | 2012-02-08 | Alnylam Pharmaceuticals Inc. | Rnai modulation of mll-af4 and uses thereof |
| US8053186B2 (en) * | 2007-06-15 | 2011-11-08 | The Ohio State University Research Foundation | Oncogenic ALL-1 fusion proteins for targeting Drosha-mediated microRNA processing |
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- 2005-12-14 US US11/303,367 patent/US7361752B2/en not_active Expired - Lifetime
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- 2005-12-14 JP JP2007546979A patent/JP2008523157A/ja active Pending
- 2005-12-14 AU AU2005316384A patent/AU2005316384B2/en not_active Expired
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- 2011-09-22 JP JP2011208167A patent/JP2011254840A/ja not_active Withdrawn
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| US7674779B2 (en) | 2010-03-09 |
| AU2005316384B2 (en) | 2012-02-09 |
| AU2005316384A1 (en) | 2006-06-22 |
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| WO2006066158A3 (en) | 2007-04-19 |
| US20080233584A1 (en) | 2008-09-25 |
| EP1824872B1 (en) | 2012-02-08 |
| US20120010267A1 (en) | 2012-01-12 |
| US20100256218A1 (en) | 2010-10-07 |
| JP2008523157A (ja) | 2008-07-03 |
| US8034793B2 (en) | 2011-10-11 |
| JP2011254840A (ja) | 2011-12-22 |
| EP1824872A2 (en) | 2007-08-29 |
| US7361752B2 (en) | 2008-04-22 |
| WO2006066158A2 (en) | 2006-06-22 |
| US20060166918A1 (en) | 2006-07-27 |
| EP1824872A4 (en) | 2008-11-26 |
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