Optimisation of genomic editing for application to gene therapy of monogenic diseases (Q3167757): Difference between revisions
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(Created claim: summary (P836): The ideal medicine for the treatment of monogenic diseases would be one that could correct the mutations that cause the pathology. This objective is something that is recently being addressed thanks to the development of various genomic editing systems, especially those based on specific nucleases (NE) such as ZFNs or the CRISPR system. These techniques allow to rewrite the DNA sequence of target cells in a sufficiently effective and specific wa...) |
(Changed label, description and/or aliases in en: translated_label) |
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Optimisation of genomic editing for application to gene therapy of monogenic diseases | |||
Revision as of 16:23, 12 October 2021
Project Q3167757 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Optimisation of genomic editing for application to gene therapy of monogenic diseases |
Project Q3167757 in Spain |
Statements
121,600.0 Euro
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152,000.0 Euro
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80.0 percent
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1 January 2019
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31 March 2022
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FUNDACION PUBLICA ANDALUZA PROGRESO Y SALUD
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37°10'24.60"N, 3°35'58.31"W
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18087
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El medicamento ideal para el tratamiento de las enfermedades monogénicas sería aquel que pudiera corregir las mutaciones que causan la patología. Este objetivo es algo que se está abordando recientemente gracias al desarrollo de diversos sistemas de edición genómica, especialmente aquellos basados en las nucleasas específicas (NE) como las ZFNs o el sistema CRISPR. Estas técnicas permiten re-escribir la secuencia de ADN de las células diana de una manera lo suficientemente eficaz y específica como para poder pensar en su utilización como herramienta terapéutica. En este proyecto nos centraremos en primer lugar en mejorar la eficacia y seguridad de la edición genómica ex vivo e in vivo para después diseñar estrategias terapéuticas para la enfermedad de Pompe, una glucogenosis causada por mutaciones en el gen que codifica para la enzima lisosomal alfa-glucosidasa ácida (GAA), responsable del catabolismo del glucógeno a glucosa. Para el abordaje ex vivo se procederá a comparar diferentes sistemas de entrega de las NE y los ADN donadores para conseguir editar el genoma de las células madre hematopoyéticas (HSCs) para que sobre-expresen GAA. Estas HSCs editadas serán utilizadas como caballo de Troja para hacer llegar GAA a los diferentes tejidos a la vez que permitiría evitar una respuesta inmune de los pacientes frente a esta proteína. Para mejorar la edición genómica in vivo se utilizarán diferentes serotipos de vectores adenoasociados (AAV) expresando las NE y/o conteniendo el ADN donador con la finalidad de reparar la expresión normal de GAA en hígado y músculo. Ambas estrategias se utilizarán por separado o combinadas en un modelo murino de la enfermedad de Pompe. En todas las estrategias estudiaremos la eficacia terapéutica, la generación de respuesta inmune frente a GAA, así como la seguridad de los procedimientos (Spanish)
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The ideal medicine for the treatment of monogenic diseases would be one that could correct the mutations that cause the pathology. This objective is something that is recently being addressed thanks to the development of various genomic editing systems, especially those based on specific nucleases (NE) such as ZFNs or the CRISPR system. These techniques allow to rewrite the DNA sequence of target cells in a sufficiently effective and specific way to be able to think about its use as a therapeutic tool. In this project we will focus first on improving the effectiveness and safety of genomic editing ex vivo and in vivo and then design therapeutic strategies for Pompe’s disease, a glycogenosis caused by mutations in the gene that encodes for the enzyme lysosomal alpha-glucosidase acid (GAA), responsible for catabolism of glycogen to glucose. For the ex vivo approach, different delivery systems of NEs and donor DNA will be compared in order to edit the hematopoietic stem cell genome (HSCs) to over-express GAA. These edited HSCs will be used as a troja horse to get GAA to the different tissues while avoiding an immune response of patients to this protein. To improve genomic editing in vivo, different adenoassociated vector serotypes (AAVs) will be used by expressing NEs or containing donor DNA in order to repair the normal expression of GAA in liver and muscle. Both strategies will be used separately or combined in a murine model of Pompe’s disease. In all strategies we will study therapeutic efficacy, the generation of immune response to GAA, as well as the safety of procedures (English)
12 October 2021
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Granada
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Identifiers
PI18_00337
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