{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ge R"],"funding":["National Natural Science Foundation of China","National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["4683"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12092677"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["Oligonucleotide-based medicine faces challenges in efficiently crossing the blood-brain barrier and rapidly reducing toxic proteins. To address these challenges, here we establish an integrated modality, brain-penetrant DNA nanoflowers incorporated with oligonucleotide-based proteolysis targeting chimeras. Using FUS as a proof-of-concept, mutations of which cause frontotemporal dementia and amyotrophic lateral sclerosis, we demonstrate that a FUS-engaging RNA oligonucleotide crosslinked to a ligand for Cereblon efficiently degrade FUS and its cytoplasmic disease-causing mutants through a ubiquitin-proteasomal pathway. The DNA nanoflower contains hundreds of oligonucleotide binding sites and transferrin receptor-engaging aptamers, allowing efficient loading of the oligonucleotide-based degr"],"journal":["Nature communications"],"pubmed_title":["DNA nanoflower Oligo-PROTAC for targeted degradation of FUS to treat neurodegenerative diseases."],"pmcid":["PMC12092677"],"funding_grant_id":["32200613","32270892"],"pubmed_authors":["Zhang F","Pan W","Cao M","Li J","Zhou P","Zhu Y","Liu M","Xuan C","Chen M","Ni G","Li Q","Zhang L","Yu H","Xie S","Ge R","Huang S","Yang Z","Zang J","Wu S","Zhou J"],"additional_accession":[]},"is_claimable":false,"name":"DNA nanoflower Oligo-PROTAC for targeted degradation of FUS to treat neurodegenerative diseases.","description":"Oligonucleotide-based medicine faces challenges in efficiently crossing the blood-brain barrier and rapidly reducing toxic proteins. To address these challenges, here we establish an integrated modality, brain-penetrant DNA nanoflowers incorporated with oligonucleotide-based proteolysis targeting chimeras. Using FUS as a proof-of-concept, mutations of which cause frontotemporal dementia and amyotrophic lateral sclerosis, we demonstrate that a FUS-engaging RNA oligonucleotide crosslinked to a ligand for Cereblon efficiently degrade FUS and its cytoplasmic disease-causing mutants through a ubiquitin-proteasomal pathway. The DNA nanoflower contains hundreds of oligonucleotide binding sites and transferrin receptor-engaging aptamers, allowing efficient loading of the oligonucleotide-based degr","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 May","modification":"2026-06-01T05:21:00.652Z","creation":"2026-04-08T09:30:26.943Z"},"accession":"S-EPMC12092677","cross_references":{"pubmed":["40394046"],"doi":["10.1038/s41467-025-60039-2"]}}