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Series GSE133554 Query DataSets for GSE133554
Status Public on Nov 15, 2019
Title CRISPRa-mediated Kcna1 upregulation decreases neuronal excitability and suppresses seizures in a rodent model of temporal lobe epilepsy [I]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Epilepsy is a major health burden, calling for new mechanistic and therapeutic insights. CRISPR–mediated gene editing shows promise to cure genetic pathologies, although hitherto it has mostly been applied ex-vivo. Its translational potential for treating non-genetic pathologies is still unexplored. Furthermore, neurological diseases represent an important challenge for the application of CRISPR, because of the need in many cases to manipulate gene function of neurons in situ. A variant of CRISPR, CRISPRa, offers the possibility to modulate the expression of endogenous genes by directly targeting their promoters. We asked if this strategy can be effective to treat acquired focal epilepsy. We applied a doxycycline-inducible CRISPRa technology to increase the expression of the potassium channel gene Kcna1 (encoding Kv1.1) in mouse hippocampal excitatory neurons. CRISPRa-mediated Kv1.1 upregulation led to a substantial decrease in neuronal excitability. Continuous video-EEG telemetry showed that AAV9-mediated delivery of CRISPRa, upon doxycycline administration, decreased spontaneous generalized tonic-clonic seizures in a model of temporal lobe epilepsy. The focal treatment minimizes concerns about off-targets effects in other organs and brain areas. This study provides the proof of principle for a translational CRISPR-based approach to treat neurological diseases characterized by abnormal circuit excitability.
 
Overall design 6x Epileptic treated with sgLacZ, 6x Epileptic treated with sgKcna1, and 5x Control treated with sgLacZ adult mouse hippocampi
 
Contributor(s) Colasante G, Massimino L, Lignani G, Broccoli V
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Submission date Jun 30, 2019
Last update date Nov 17, 2019
Contact name Luca Massimino
E-mail(s) admin@lucamassimino.com
Phone 3389039500
Organization name Ospedale San Raffaele
Department Gastroenterology
Street address Via Olgettina, 58
City Milano
State/province MI
ZIP/Postal code 20100
Country Italy
 
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (17)
GSM3911845 Adult mouse hippocampus, Epileptic treated with sgLacZ 4
GSM3911846 Adult mouse hippocampus, Epileptic treated with sgLacZ 5
GSM3911847 Adult mouse hippocampus, Epileptic treated with sgLacZ 6
This SubSeries is part of SuperSeries:
GSE133930 CRISPRa-mediated Kcna1 upregulation decreases neuronal excitability and suppresses seizures in a rodent model of temporal lobe epilepsy
Relations
BioProject PRJNA551881
SRA SRP212656

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
GSE133554_RAW.tar 5.8 Mb (http)(custom) TAR (of TAB)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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