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CRISPRa-mediated Kcna1 upregulation decreases neuronal excitability and suppresses seizures in a rodent model of temporal lobe epilepsy

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE133930 | GEO | 2019/11/15

REPOSITORIES: GEO

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CRISPRa-mediated Kcna1 upregulation decreases neuronal excitability and suppresses seizures in a rodent model of temporal lobe epilepsy [II]

Project description: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.

2019-11-15 | GSE133929 | GEO

CRISPRa-mediated Kcna1 upregulation decreases neuronal excitability and suppresses seizures in a rodent model of temporal lobe epilepsy [I]

2019-11-15 | GSE133554 | GEO

CRISPRa-mediated Kcna1 upregulation decreases neuronal excitability and suppresses seizures in a rodent model of temporal lobe epilepsy

Project description:CRISPRa-mediated Kcna1 upregulation decreases neuronal excitability and suppresses seizures in a rodent model of temporal lobe epilepsy

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Project description:CRISPRa-mediated Kcna1 upregulation decreases neuronal excitability and suppresses seizures in a rodent model of temporal lobe epilepsy [I]

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CRISPRa-mediated Kcna1 upregulation decreases neuronal excitability and suppresses seizures in a rodent model of temporal lobe epilepsy [II]

Project description:CRISPRa-mediated Kcna1 upregulation decreases neuronal excitability and suppresses seizures in a rodent model of temporal lobe epilepsy [II]

| PRJNA553149 | ENA