PXD065583

PXD065583 is an original dataset announced via ProteomeXchange.

Title	Deciphering the impact of antisense oligonucleotide activity on RNA and protein level
Description	Most classes of oligonucleotide drugs (OND) target RNA with the aim to modify expression on the protein level. The majority of studies evaluating on- and unintended off-target (OffT) activity of ONDs focus on transcriptomics assessment, especially for global changes. The lack of global proteomics studies for ASOs can be attributed to previous bottlenecks, such as high cost, insufficient depth, sensitivity, throughput and variable protein half-life. Here, we leveraged recent breakthroughs in proteomics technology to overcome these bottlenecks and systematically dissect global activity on RNA and protein level upon ASO transfection in HepG2 cells. First, we discovered that safe and liver toxic ASOs showed distinct expression patterns in both RNA sequencing and proteomics datasets. Interestingly, we observed similar ASO on- and OffT activity time courses for RNA and protein, despite longer reported protein half-life. Finally, we distinguished higher numbers of in silico predicted OffTs affected on RNA than protein level, which correlated with most predicted OffTs showing a larger reduction on RNA level. We believe that these results demonstrate the importance of studying OND activity on both RNA and protein level and anticipate that this study will stimulate similar work to expand our current understanding of ONDs.
HostingRepository	PRIDE
AnnounceDate	2026-03-18
AnnouncementXML	Submission_2026-03-18_06:56:26.998.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anthony Iannetta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF fleX

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-28 20:33:16	ID requested
⏵ 1	2026-03-18 06:56:27	announced

10.1093/NARMME/UGAG016;

submitter keyword: antisense oligonucleotides, off-target profiling

Anthony Iannetta
contact affiliation	AstraZeneca
contact email	anthony.iannetta@astrazeneca.com
lab head
Anthony Iannetta
contact affiliation	AstraZeneca
contact email	anthony.iannetta@astrazeneca.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065583
     1. Label: PRIDE project
     2. Name: Deciphering the impact of antisense oligonucleotide activity on RNA and protein level