PXD027804-1

PXD027804 is an original dataset announced via ProteomeXchange.

Title	Antisense oligonucleotide activity in tumour cells is influenced by intracellular LBPA distribution and 6 extracellular vesicles recycling
Description	Next generation modified antisense oligonucleotides (ASOs) are commercially approved new therapeutic modalities, yet poor productive uptake and endosomal entrapment in tumour cells limit their broad application. We compared intracellular traffic of anti KRAS antisense oligonucleotide (AZD4785) in good and poor productive uptake tumour cells, PC9 and LK2 respectively. We found that the majority of AZD4785 is rapidly delivered to CD63+ late endosomes (LE) in both cell lines. Importantly, lysobisphosphatidic acid (LBPA) that triggers ASO LE escape is presented in CD63+ LE in PC9 but not in LK2 cells. Moreover, both cells recycle AZD4785 in the extracellular vesicles (EVs) however AZD4785 quantification by advanced mass spectrometry and proteomic analysis revealed that LK2 recycles more AZD4785 and RNA-binding proteins. Finally, stimulating LBPA intracellular production or blocking EV recycling enhanced AZD4785 activity in LK2 but not in PC9 cells thus offering novel strategy to possibly enhance ASO potency in poor productive uptake tumour cells.
HostingRepository	PRIDE
AnnounceDate	2021-11-10
AnnouncementXML	Submission_2021-11-10_07:44:00.157.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nitin Rustogi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-09 06:33:08	ID requested
⏵ 1	2021-11-10 07:44:00	announced

Dataset with its publication pending

submitter keyword: Antisense Oligonucletides, LC-MS/MS

Nicholas J Bond
contact affiliation	Biopharmaceutical development, R&D, AstraZeneca, Cambridge, UK
contact email	nick.bond@astrazeneca.com
lab head
Nitin Rustogi
contact affiliation	Astrazeneca
contact email	nitin.rustogi@astrazeneca.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/11/PXD027804

PRIDE project URI

• PRIDE
  1. PXD027804
     1. Label: PRIDE project
     2. Name: Antisense oligonucleotide activity in tumour cells is influenced by intracellular LBPA distribution and 6 extracellular vesicles recycling