PXD072230

PXD072230 is an original dataset announced via ProteomeXchange.

Title	Non-viral in situ gene editing effectively and safely rescues congenital ichthyosis-causing mutations in human skin
Description	Autosomal recessive congenital ichthyosis (ARCI) refers to a group of rare, highly debilitating skin disorders which significantly impair patients’ quality of life and lack any effective treatment options. Here, we report clinically-relevant in situ correction of the most common ARCI-causing mutation TGM1 c.877-2A>G, a splice-site aberration, in human disease models. Targeted skin barrier modulation followed by topical application of the cytosine base editor eTD packaged into lipid nanoparticles yielded functional restoration of ~30% of wild-type transglutaminase 1 activity in skin tissue. Toxicity studies and comprehensive off-target analysis demonstrated an excellent safety profile even after repeated application, without systemic distribution of the lipid nanoparticles or the genetic cargo as determined via highly-sensitive methods including DESI metabolic imaging. This study presents comprehensive preclinical data on the feasibility of in situ gene correction of genodermatoses-causing mutations showcasing its therapeutic potential and paving the way for curative next-generation treatments for severe genetic skin diseases.
HostingRepository	PRIDE
AnnounceDate	2026-01-23
AnnouncementXML	Submission_2026-01-23_13:50:39.787.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fabian Coscia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Ultra 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-19 19:30:54	ID requested
⏵ 1	2026-01-23 13:50:40	announced

10.1016/J.STEM.2026.01.001;

submitter keyword: ARCI

autosomal recessive congenital ichthyosis

skin

TGM1

tissue

Fabian Coscia
contact affiliation	Max Delbrück Center for Molecular Medicine Berlin
contact email	fabian.coscia@mdc-berlin.de
lab head
Fabian Coscia
contact affiliation	Max Delbrück Center
contact email	fabian.coscia@mdc-berlin.de
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/2026/01/PXD072230

PRIDE project URI

• PRIDE
  1. PXD072230
     1. Label: PRIDE project
     2. Name: Non-viral in situ gene editing effectively and safely rescues congenital ichthyosis-causing mutations in human skin