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Series GSE240935 Query DataSets for GSE240935
Status Public on Dec 20, 2023
Title Durable and efficient gene silencing in vivo by hit-and-run epigenome editing [targetBSseq_offTargets]
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary Permanent epigenetic silencing with programmable editors equipped with transcriptional repressors holds great promise for the treatment of human diseases. However, to unlock its full therapeutic potential, a formal proof of durable epigenetic silencing upon transient editors’ delivery in vivo is needed. To this end, we targeted here Pcsk9, a hepatocyte-expressed gene involved in cholesterol homeostasis. In vitro screening of different editors’ designs indicated zinc finger proteins as the best-performing DNA binding platform to efficiently silence murine Pcsk9, with minimal genome-wide transcriptional and epigenetic perturbations. A single administration of lipid nanoparticles loaded with the editors’ mRNAs halved circulating levels of Pcsk9 for nearly 1 year in mice. Notably, Pcsk9 silencing and accompanying epigenetic repressive marks persisted following forced also upon liver regeneration, further corroborating heritability of the newly installed epigenetic state. This study lays the foundation for the development of in vivo therapeutics modalities based on epigenetic silencing.
 
Overall design Comparative analysis of Arid1b e Shroom1 in vitro DMR methylation status from hepatocytes treated with ZFP-ETRs targeting Pcsk9 and PBS
 
Contributor(s) Cappelluti MA, Poeta VM, Valsoni S, Quarato P, Merelli I, Lombardo AL
Citation(s) 38418872
Submission date Aug 16, 2023
Last update date Mar 20, 2024
Contact name Sara Valsoni
E-mail(s) [email protected]
Organization name SR-TIGET
Department TIGET
Street address via Olgettina 60
City Milano
State/province MI
ZIP/Postal code 20132
Country Italy
 
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (6)
GSM7712391 ZFP-ETRs against Pcsk9 treated hepatocytes, replicate 1
GSM7712392 ZFP-ETRs against Pcsk9 treated hepatocytes, replicate 2
GSM7712393 ZFP-ETRs against Pcsk9 treated hepatocytes, replicate 3
This SubSeries is part of SuperSeries:
GSE226209 Durable and efficient gene silencing in vivo by hit-and-run epigenome editing
Relations
BioProject PRJNA1005913

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE240935_RAW.tar 60.0 Kb (http)(custom) TAR (of COV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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