PXD057965

PXD057965 is an original dataset announced via ProteomeXchange.

Title	Identification of a 144-amino-acid Scaffold Protein for Extracellular Vesicle Engineering
Description	Extracellular vesicles (EVs) have emerged as promising drug-delivery vehicles. Genetic engineering of a membrane-bound, EV-sorting scaffold protein empowers these cell-borne nanosized vesicles by installing targeting moieties on the surface and enriching therapeutic cargo in the lumen. However, the choice of scaffold proteins with a simple structure and short sequence is scarce. Here, we conduct mass-spectrometry-based proteomic studies, identify 15 candidate proteins with EV-sorting properties, and examine their capability as the scaffold protein. ENPP1 stands out from our screening, outperforming the widely used EV-sorting proteins PTGFRN and Lamp2b with high abundance, homogeneity, stability, and engineerability. In particular, a 144-amino acid truncated version of ENPP1, called EN144 here, demonstrates high-density loading of cargos, including peptides, proteins, and mRNAs. Based on this finding, we engineer decoy EVs expressing IL-6 signal transducer (IL6ST, a.k.a. gp130) fused with EN-144, EN144-EVhgp130, to inhibit the IL-6 trans-signaling pathway. The resulting decoy EVs elicit potent anti-inflammatory effects and improve the survival rate of septic mice. Chondrocyte-targeting EN144-EVhgp130 ameliorates inflammation and remodels the synovial tissue microenvironment of cartilage in a rat model of osteoarthritis (OA), surpassing tocilizumab (TCZ), the clinically approved humanized anti-interleukin-6 receptor (IL-6R) antibody. Altogether, we report the identification and verification of EN144 as one of the smallest and simplest scaffold proteins for EV engineering and showcase systematic and local administrations of EN144-engineered decoy EVs for treating inflammatory diseases.
HostingRepository	PRIDE
AnnounceDate	2026-04-27
AnnouncementXML	Submission_2026-04-26_16:37:40.043.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wenjing Yan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	carbamoylated residue; acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-17 03:28:40	ID requested
⏵ 1	2026-04-26 16:37:41	announced

Yan W, Wang S, Hao H, Lin H, Wang C, Xie S, Zhang X, Lu Y, Ding X, Chen X, Liu H, Zhang G, Wei D, Ma C, Tang C, Li X, Yu B, Hu J, Gu Z, Yu EY, Li W, Xia J, Zhang H, Extracellular vesicle engineering using a small scaffold protein. Nat Commun, 17(1):(2026) [pubmed]

10.1038/s41467-026-70451-x;

submitter keyword: Expi293F-EVs, LC-S/MS

Wang shi zhi
contact affiliation	Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
contact email	shizhiwang2009@seu.edu.cn
lab head
Wenjing Yan
contact affiliation	Southeast university
contact email	13915963122@163.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/2026/04/PXD057965

PRIDE project URI

• PRIDE
  1. PXD057965
     1. Label: PRIDE project
     2. Name: Identification of a 144-amino-acid Scaffold Protein for Extracellular Vesicle Engineering