PXD064937

PXD064937 is an original dataset announced via ProteomeXchange.

Title	Removing the mutant: Allele-selective knock-out ameliorates VWD type 2 in patient-derived ECFCs
Description	Treatment of von Willebrand disease (VWD) has been topic of discussions and research for several decades. The (genetic) heterogeneity of the inherited bleeding disorder remains one of the biggest obstacles for proper treatment, as well as the high costs of (recombinant) factor concentrates of VWF. In this study we present a personalized gene therapy approach for heterozygous VWD type 2 patients that has been inspired by previous research on allele-selective siRNA targeting of mutant VWF. However, instead of siRNAs, we designed allele-selective gRNAs that are capable to selectively remove the allele carrying the pathogenic variant using CRISPR-Cas9. By targeting a common heterozygous SNP on the mutant allele, the strategy holds the possibility to find a broader application among patients, while being personalized at the same time. The results in our ex vivo model of patient-derived endothelial colony forming cells (ECFCs) show a strong allele-selectivity and a rescue of the disease phenotype in these cells. Proteomic analysis and next generation sequencing (NGS) validate the phenotypic observations and suggest this approach as a promising gene therapeutic strategy for future treatment of heterozygous VWD patients.
HostingRepository	PRIDE
AnnounceDate	2026-03-09
AnnouncementXML	Submission_2026-03-09_03:44:13.525.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stijn Groten
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-12 06:33:15	ID requested
⏵ 1	2026-03-09 03:44:14	announced

B, ä, r I, Groten SA, Barraclough A, B, ü, rgisser PE, van Kwawegen C, Lenting PJ, van Moort I, Eikenboom JCJ, Leebeek FWG, Voorberg J, van den Biggelaar M, Bierings R, Allele-selective disruption of pathogenic VWF variants in type 2 von Willebrand disease using CRISPR/Cas9. Blood Adv, 10(5):1429-1443(2026) [pubmed]

10.1182/bloodadvances.2025018760;

submitter keyword: VWD, peptide analysis, endothelial cells, variant detection, allele knockout

Maartje van den Biggelaar, PhD
contact affiliation	Proteomics Group, Department of molecular hemastasis, Sanquin Research, Amsterdam, the Netherlands
contact email	m.vandenbiggelaar@sanquin.nl
lab head
Stijn Groten
contact affiliation	Sanquin Research
contact email	s.groten@sanquin.nl
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/2026/03/PXD064937

PRIDE project URI

• PRIDE
  1. PXD064937
     1. Label: PRIDE project
     2. Name: Removing the mutant: Allele-selective knock-out ameliorates VWD type 2 in patient-derived ECFCs