PXD063296-1

PXD063296 is an original dataset announced via ProteomeXchange.

Title	Small-molecule inhibitors of CRISPR/Cas13 enable versatile control of RNA knockdown in mammalian cells
Description	Abstract: CRISPR/Cas13 has emerged as a leading platform for carrying out RNA knockdown and editing experiments, and presents an attractive therapeutic alternative to DNA editing technologies. However, strategies to directly modulate its activity in a fast, reliable, and generalizable manner are lacking. Here, we carry out a high- throughput screen to identify small-molecule inhibitors of LwaCas13a in order to enable titration of RNA knockdown and spatiotemporal control. We identify 6 lead hits that potently inhibit on-target and collateral Cas13 RNA cleavage but not pre-crRNA processing activity. We show that these compounds act via non-competitive and mixed mechanisms, and are selective for a subset of Cas13 homologs. Moreover, we demonstrate that two compounds, CID5483251 and HTS10308, inhibit RNA knockdown by exogenous Cas13 in mammalian cells at subtoxic doses, and can be used to tune mRNA and corresponding protein levels in a dose- and time-dependent manner. This study delivers new tools for achieving versatile control of Cas13 activity in mammalian cells, and establishes a foundation for the design of additional Cas13 inhibitors.
HostingRepository	PRIDE
AnnounceDate	2026-07-17
AnnouncementXML	Submission_2026-07-17_15:04:02.180.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Venita Sitahal
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	SELECT SERIES Cyclic IMS

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-24 14:51:24	ID requested
⏵ 1	2026-07-17 15:04:02	announced

Dataset with its publication pending

submitter keyword: CRISPR/CAS13, Cas13 inhibitors, LwaCas13a, HDX-MS

Derek Wilson
contact affiliation	Department of Chemistry, Wilson Lab, York University, Canada
contact email	dkwilson@yorku.ca
lab head
Venita Sitahal
contact affiliation	York University
contact email	vsitahal@yorku.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063296
     1. Label: PRIDE project
     2. Name: Small-molecule inhibitors of CRISPR/Cas13 enable versatile control of RNA knockdown in mammalian cells