PXD072066

PXD072066 is an original dataset announced via ProteomeXchange.

Title	LNP formulations for efficient hepatic delivery studied with an in-vivo endosomal escape assay
Description	Endosomal escape is a central barrier to efficient nucleic acid delivery by lipid nanoparticles (LNPs) and remains challenging to quantify in vivo. We report a library of branched ionizable phospholipids (BiPs) that markedly enhance mRNA delivery to the liver. The lead candidate BiP-20 outperformed the clinical benchmark LP01 by 4-fold for CRISPR–Cas9 editing of the TTR gene at low dose with rapid pharmacokinetics. To quantify the endosomal escape kinetics of BiP-20, we used LysoTag mice, which allow immunoisolation of liver lysosomes, and our Lysosomal Barcoding method, finding that ~9% of BiP-20 LNPs reach the cytosol within 30 minutes of administration. Lysosomal proteomics revealed mechanistic regulators of escape and BiP-20–induced alterations in endosomal maturation and recycling pathways. Loss of Rab7, a mediator of late endosomal maturation, increased LNP escape. These findings provide a potent class of ionizable lipids for RNA delivery, a method to quantify endosomal escape in vivo, and mechanistic insight into the endolysosomal determinants of LNP trafficking.
HostingRepository	PRIDE
AnnounceDate	2026-01-20
AnnouncementXML	Submission_2026-01-20_13:01:51.775.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-16 18:31:32	ID requested
⏵ 1	2026-01-20 13:01:52	announced

Dataset with its publication pending

submitter keyword: lipid nanoparticle, mass spectrometry, endosomal escape, quantitative proteomics, gene editing

Gaurav Sahay
contact affiliation	Department of Pharmaceutical Sciences Oregon State University College of Pharmacy Portland, OR 97301 USA
contact email	sahay@ohsu.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD072066
     1. Label: PRIDE project
     2. Name: LNP formulations for efficient hepatic delivery studied with an in-vivo endosomal escape assay