PXD049388

PXD049388 is an original dataset announced via ProteomeXchange.

Title	Examining the modality-dependent target specificity of bioPROTACs by analysing global proteome changes following mRNA-encoded or recombinant protein biodegrader delivery.
Description	Proteolysis targeting chimeras (PROTACs) have surged in popularity as a drug modality owing to their ability to degrade pathogenic proteins. Despite their advantages over conventional inhibitors, PROTAC discovery still requires high-affinity warheads, but ligands for undruggable proteins are difficult to develop. As an alternative, protein based biological PROTACs (bioPROTACs) have been explored as a potential therapeutic. Since their substrate affinity is conferred by small-protein scaffolds, bioPROTACs are more easily developed for undruggable targets. Currently, bioPROTAC delivery is accomplished via electroporation, microinjection, or DNA/mRNA transfection, but these methods are either poorly translated to the clinic or suffer from manufacturing disadvantages. We developed a method to encapsulate and deliver recombinant bioPROTACs intracellularly using lipid nanoparticles. This study aims at evaluating differential degradation patterns between the same bioPROTAC delivered either as protein or as mRNA. To accomplish this, Ras-targeting bioPROTAC protein or mRNA were delivered to HEK293T cells or 8 hours. On- and off- target degradation was studied by LC-MS/MS shotgun proteomics. A label free based quantitative approach was used to identify significantly altered proteins in either treatment group. Gene ontology (GO) biological process and molecular function analyses were performed on significantly degraded proteins to determine target specificity for protein and mRNA bioPROTAC modalities.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:47:40.258.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Tsourkas
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-14 11:21:52	ID requested
1	2024-06-27 07:34:49	announced
⏵ 2	2024-10-22 06:47:40	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: recombinant protein, proteomics, Lipid nanoparticle,PROTAC, GTPase, Mass spectrometry, Ras, drug delivery, bioPROTAC, mRNA, cytosolic delivery, KRAS

Andrew Tsourkas
contact affiliation	Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA
contact email	atsourk@seas.upenn.edu
lab head
Andrew Tsourkas
contact affiliation	Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA
contact email	atsourk@seas.upenn.edu
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/2024/06/PXD049388

PRIDE project URI

• PRIDE
  1. PXD049388
     1. Label: PRIDE project
     2. Name: Examining the modality-dependent target specificity of bioPROTACs by analysing global proteome changes following mRNA-encoded or recombinant protein biodegrader delivery.