{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Zeballos C MA"],"funding":["NIBIB NIH HHS","NINDS NIH HHS","NIGMS NIH HHS"],"pubmed_abstract":["The TDP-43 proteinopathies, which include amyotrophic lateral sclerosis and frontotemporal dementia, are a devastating group of neurodegenerative disorders that are characterized by the mislocalization and aggregation of TDP-43. Here we demonstrate that RNA-targeting CRISPR effector proteins, a programmable class of gene silencing agents that includes the Cas13 family of enzymes and Cas7-11, can be used to mitigate TDP-43 pathology when programmed to target ataxin-2, a modifier of TDP-43-associated toxicity. In addition to inhibiting the aggregation and transit of TDP-43 to stress granules, we find that the <i>in vivo</i> delivery of an ataxin-2-targeting Cas13 system to a mouse model of TDP-43 proteinopathy improved functional deficits, extended survival, and reduced the severity of neuro"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2023.04.07.536072"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10104115"],"repository":["biostudies-literature"],"pubmed_title":["Mitigating a TDP-43 proteinopathy by targeting ataxin-2 using RNA-targeting CRISPR effector proteins."],"pmcid":["PMC10104115"],"funding_grant_id":["U01 NS122102","T32 EB019944","R01 GM141296","R01 NS123556"],"pubmed_authors":["Gaj T","Zeballos C MA","Ahsan NS","Powell JE","Smith TJ","Zhang S","Moore HJ"],"additional_accession":[]},"is_claimable":false,"name":"Mitigating a TDP-43 proteinopathy by targeting ataxin-2 using RNA-targeting CRISPR effector proteins.","description":"The TDP-43 proteinopathies, which include amyotrophic lateral sclerosis and frontotemporal dementia, are a devastating group of neurodegenerative disorders that are characterized by the mislocalization and aggregation of TDP-43. Here we demonstrate that RNA-targeting CRISPR effector proteins, a programmable class of gene silencing agents that includes the Cas13 family of enzymes and Cas7-11, can be used to mitigate TDP-43 pathology when programmed to target ataxin-2, a modifier of TDP-43-associated toxicity. In addition to inhibiting the aggregation and transit of TDP-43 to stress granules, we find that the <i>in vivo</i> delivery of an ataxin-2-targeting Cas13 system to a mouse model of TDP-43 proteinopathy improved functional deficits, extended survival, and reduced the severity of neuro","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Aug","modification":"2025-04-04T10:21:53.418Z","creation":"2025-02-19T02:38:21.618Z"},"accession":"S-EPMC10104115","cross_references":{"pubmed":["37066174"],"doi":["10.1101/2023.04.07.536072"]}}