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PXD068788-1

PXD068788 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIdentification and functional validation of intracellular protein partners of phosphorothioate-splice switching oligonucleotides through AP-MS
DescriptionDespite growing interest in therapeutic antisense oligonucleotides (ASOs), the mechanisms governing their intracellular trafficking remain poorly understood. This study investigates the intracellular protein partners of splice-switching oligonucleotides (SSOs) modified with phosphorothioate (PS) backbones of three different chemistries: tricycloDNA (tcDNA), locked nucleic acid (LNA), and 2'-O-methoxyethyl (2′MOE). The SSO studied here targets the exon 51 of the dystrophin pre-mRNA (SSOEx51), as part of an exon skipping strategy for Duchenne muscular dystrophy (DMD). Pulldowns were performed using lysates from differentiated human muscle cells carrying a deletion in the exon 52 of the DMD gene (KM571). Biotinylated SSOs were immobilized on streptavidin-coated magnetic beads, and interacting proteins were captured and identified by nanoLC-MS/MS. In addition to analyzing the effect of different chemistries of ASOs on protein binding, we also evaluated the impact of sequence variation by comparing two additional tcDNA chemistry sequences (named TSB-T3 and TSB-C1). Finally, to enable enrichment analyses, we performed a characterization of the whole proteome of KM571 cells.
HostingRepositoryPRIDE
AnnounceDate2026-01-20
AnnouncementXMLSubmission_2026-01-20_09:19:23.584.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGuilhem Clary
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListcarbamoylated residue; acetylated residue; monohydroxylated residue
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-09-24 15:41:48ID requested
12026-01-20 09:19:24announced
Publication List
10.1016/J.OMTN.2026.102832;
Keyword List
submitter keyword: Antisense oligonucleotides (ASOs)
phosphorothioate (PS)
splice switching oligonucleotides (SSOs)
Duchenne muscular dystrophy (DMD)
exon skipping
protein-oligonucleotide interaction
Affinity purification mass spectrometry (AP-MS)
Contact List
Aurélie GOYENVALLE
contact affiliationUniversité Paris-Saclay, UVSQ, Inserm, END-ICAP, 78000 Versailles, France
contact emailaurelie.goyenvalle@uvsq.fr
lab head
Guilhem Clary
contact affiliationIstitut Cochin
contact emailguilhem.clary@inserm.fr
dataset submitter
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Dataset FTP location
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