Patents Assigned to Koninklijke Nederlandse Akademie van Wetenschappen
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Publication number: 20240124869Abstract: The invention pertains to an ex vivo method for increasing expression of at least one of gamma globin 1 (HBG1) and 2 (HBG2). The method can be used for the treatment or prevention of a haemoglobinopathy. The method comprises a step of introducing a first and a second site-specific endonuclease into a cell, wherein the first and second site-specific endonuclease generate a first and a second double stranded break in a chromosome, thereby generating a first, an intervening second and a third chromosomal fragment, wherein i) the first fragment comprises an beta globin locus control region (LCR) a functional fragment thereof; and ii) the third fragment comprises a sequence encoding at least one of HBG1 and HBG2. The length of the second intervening fragment is at least about 5 kb, and wherein joining the first fragment to the third fragment results in operably linking the beta globin LCR to the sequence encoding at least one of HBG1 and HBG2, thereby increasing at least one of HBG1 and HBG2 protein expression.Type: ApplicationFiled: February 11, 2022Publication date: April 18, 2024Applicant: Koninklijke Nederlandse Akademie van WetenschappenInventor: Wouter Leonard DE LAAT
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Publication number: 20240093288Abstract: The invention pertains to method for ribosome profiling at a single cell resolution. The method comprises the steps of i) lysing a single cell; ii) digesting the RNA with a ribonuclease, thereby generating an ribosome footprint containing RNA molecules that are protected against digestion; iii) Inactivating the ribonuclease and releasing the RNA molecules from the ribosomes; iv) end repairing the released RNA; v) constructing an RNA library from the end-repaired RNA molecules; vi) size selecting part of the prepared RNA library for fragments having an insert size of about 20-40 nucleotides; vii) sequencing the size selected RNA library; and viii) determining the translatome of the single cell.Type: ApplicationFiled: November 25, 2021Publication date: March 21, 2024Applicant: Koninklijke Nederlandse Akademie van WetenschappenInventors: Alexander van Oudenaarden, Michael Vaninsberghe
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Publication number: 20240076624Abstract: The disclosure relates to methods and tools for studying enteroendocrine cells, including intestinal reporter organoids, methods and media for making said organoids, uses of said organoids, and enteroendocrine cell targets and treatments.Type: ApplicationFiled: March 31, 2021Publication date: March 7, 2024Applicant: Koninklijke Nederlandse Akademie Van WetenschappenInventors: Joep Beumer, Jens Puschhof, Johannes Carolus Clevers
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Publication number: 20230272347Abstract: The invention relates to differentiation methods for progenitor cells, e.g. mammalian epithelial stem cells, differentiation media for use in said methods, organoids and cells obtainable by said methods and uses, including therapeutic uses, thereof.Type: ApplicationFiled: January 23, 2023Publication date: August 31, 2023Applicant: Koninklijke Nederlandse Akademie Van WetenschappenInventors: Johannes Carolus Clevers, Helmuth Gehart
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Patent number: 11725184Abstract: The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.Type: GrantFiled: January 15, 2020Date of Patent: August 15, 2023Assignee: Koninklijke Nederlandse Akademie Van WetenschappenInventors: Meritxell Huch Ortega, Johannes Carolus Clevers, Sylvia Fernandez Boj
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Patent number: 11591572Abstract: The invention relates to differentiation methods for progenitor cells, e.g. mammalian epithelial stem cells, differentiation media for use in said methods, organoids and cells obtainable by said methods and uses, including therapeutic uses, thereof.Type: GrantFiled: March 1, 2017Date of Patent: February 28, 2023Assignee: Koninklijke Nederlandse Akademie Van WetenschappenInventors: Johannes Carolus Clevers, Helmuth Gehart
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Publication number: 20220340879Abstract: The invention relates to improved methods for culturing an epithelial stem cell or an organoid comprising epithelial stem cells. The invention also relates to culture media suitable for use with said methods, organoids obtainable or obtained by said methods and uses of said culture methods, media and organoids in drug discovery and validation, toxicity assays, diagnostics and therapy.Type: ApplicationFiled: May 18, 2020Publication date: October 27, 2022Applicant: Koninklijke Nederlandse Akademie van WetenschappenInventors: Willibrordus Barend Maria De Lau, Johannes Carolus Clevers
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Publication number: 20220195515Abstract: The invention relates to methods for processing an RNA sample and allows for single cell sequencing of full length total RNA. The method includes labeling the RNA sample with at least one of a barcode and a unique molecular identifier.Type: ApplicationFiled: October 29, 2019Publication date: June 23, 2022Applicant: Koninklijke Nederlandse Akademie van WetenschappenInventors: Alexander Van Oudenaarden, Fredrik Salmen
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Publication number: 20220154143Abstract: The invention relates to in vitro cell culture methods for expanding epithelial cells from head and neck tissue, including head and neck tumour tissue, to obtain organoids. The invention relates to culture media suitable for use with said methods, organoids obtainable or obtained by said methods and uses of said culture methods, media and organoids in drug discovery and validation, toxicity assays, diagnostics and therapy.Type: ApplicationFiled: March 16, 2020Publication date: May 19, 2022Applicant: Koninklijke Nederlandse Akademie Van WetenschappenInventors: Johannes Carolus Clevers, Else Driehuis
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Publication number: 20220135952Abstract: The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.Type: ApplicationFiled: August 24, 2021Publication date: May 5, 2022Applicant: Koninklijke Nederlandse Akademie Van WetenschappenInventors: Lars Norman Sachs, Jarno Drost
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Publication number: 20220088052Abstract: The present invention relates to novel treatments for treating cardiac disease involving fibro-fatty replacement, such as arrhythmogenic cardiomyopathy, atrial fibrillation, myocardial infarction and dilated cardiomyopathy. Such cardiac diseases can e.g. be caused by a mutation in a desmosomal protein such as plakophilin-2 (PKP2). The invention provides for agents for use in the prevention or treatment of such cardiac diseases, wherein the agent is at least one of: a) an agent that causes a reduction in expression in at least one TFAP2 subtype; and, b) an agent that causes a reduction in TFAP2-induced transcription. More preferably the agent is at least one of: a) an inhibitor of TFAP2; and, b) an agent that causes an increase in expression of PKP2.Type: ApplicationFiled: January 22, 2020Publication date: March 24, 2022Applicant: Koninklijke Nederlandse Akademie van WetenschappenInventors: Eva van Rooij, Arwa Obada Abdelrahman Reda Kohela
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Publication number: 20220017860Abstract: This invention relates to culture methods and media for in vitro expansion of hepatocytes, particularly primary hepatocytes; hepatocyte cultures and organoids obtainable and obtained by said methods; and uses of said hepatocyte cultures and organoids.Type: ApplicationFiled: November 26, 2019Publication date: January 20, 2022Applicant: Koninklijke Nederlandse Akademie Van WetenschappenInventors: Johannes Carolus Clevers, Huili Hu
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Publication number: 20210333266Abstract: The invention relates to an assay for diagnosing a disease or affliction that affects fluid uptake or secretion or for studying the effectiveness of one or more drugs for treating the disease or affliction, wherein the assay comprises measuring swelling of one or more organoids.Type: ApplicationFiled: May 7, 2021Publication date: October 28, 2021Applicants: UMC Utrecht Holding, B.V., Koninklijke Nederlandse Akademie van WetenschappenInventors: Jeffrey Matthijn Beekman, Johanna Florentia Dekkers, Cornelis Korstiaan Van Der Ent, Johannes Carolus Clevers
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Publication number: 20210317416Abstract: The invention relates to a liver organoid, uses thereof and method for obtaining them.Type: ApplicationFiled: March 3, 2021Publication date: October 14, 2021Applicant: Koninklijke Nederlandse Akademie van WetenschappenInventors: Meritxell Huch Ortega, Johannes Carolus Clevers
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Patent number: 11130943Abstract: The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.Type: GrantFiled: November 27, 2015Date of Patent: September 28, 2021Assignee: Koninklijke Nederlandse Akademie Van WetenschappenInventors: Lars Norman Sachs, Jarno Drost
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Publication number: 20210254017Abstract: The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.Type: ApplicationFiled: February 23, 2021Publication date: August 19, 2021Applicant: Koninklijke Nederlandse Akademie Van WetenschappenInventors: Lars Norman Sachs, Ana Gracanin, Jarno Drost
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Publication number: 20210228682Abstract: The invention relates to the fields of biochemistry, pharmacy and oncology. The invention particularly relates to the use of novel stem cell markers for the isolation of stem cells. The invention further relates to the obtained stem cells and their use in for example research or treatment, for example, for the preparation of a medicament for the treatment of damaged or diseased tissue. In one of the embodiments, the invention provides a method for obtaining (or isolating) stem cells comprising optionally preparing a cell suspension from a tissue or organ sample, contacting said cell suspension with an Lgr 6 or 5 binding compound, identify the cells bound to said binding compound, and optionally isolating the stem cells from said binding compound. The invention further relates to means suitable for cancer treatment and even more specific for the treatment of cancer by eradicating cancer stem cells.Type: ApplicationFiled: January 28, 2021Publication date: July 29, 2021Applicant: Koninklijke Nederlandse Akademie van WetenschappenInventors: Johannes Carolus Clevers, Nicholas Barker, Andrea Haegebarth, Marcus Lambertus Van de Wetering
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Publication number: 20210208131Abstract: The present invention provides co-cultures of organoids and immune cells, and methods of using these to identify agents for treating diseases.Type: ApplicationFiled: December 21, 2018Publication date: July 8, 2021Applicants: Koninklijke Nederlandse Akademie van Wetenschappen, Stichting Hubrecht Organoid TechnologyInventors: Kai Kretzschmar, Jotam Elazar Bar-Ephraim, Johannes Carolus Clevers, Sylvia Fernandez-Boj, Robert Gerhardus Jacob Vries
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Patent number: 11035852Abstract: The invention relates to an assay for diagnosing a disease or affliction that affects fluid uptake or secretion or for studying the effectiveness of one or more drugs for treating the disease or affliction, wherein the assay comprises measuring swelling of one or more organoids.Type: GrantFiled: June 8, 2018Date of Patent: June 15, 2021Assignees: UMC Utrecht Holding, B.V., Koninklijke Nederlandse Akademie van WetenschappenInventors: Jeffrey Matthijn Beekman, Johanna Florentia Dekkers, Cornelis Korstiaan Van Der Ent, Johannes C. Clevers
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Patent number: 11034935Abstract: The invention relates to a liver organoid, uses thereof and method for obtaining them.Type: GrantFiled: July 31, 2017Date of Patent: June 15, 2021Assignee: Koninklijke Nederlandse Akademie van WetenschappenInventors: Meritxell Huch Ortega, Johannes Carolus Clevers