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Antisense oligonucleotides increase Scn1a expression and reduce seizures and SUDEP incidence in a mouse model of Dravet syndrome
Antisense oligonucleotides raise Scn1a gene levels and lower seizures and sudden death in a mouse model of Dravet syndrome
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Abstract
A single dose of a lead antisense oligonucleotide reduced the incidence of electrographic seizures in a mouse model of Dravet syndrome.
- Dravet syndrome is associated with de novo variants in the SCN1A gene, leading to reduced function of sodium channel Na1.1.
- Targeted Augmentation of Nuclear Gene Output (TANGO) technology was used to enhance gene expression related to this condition.
- Antisense oligonucleotides were identified that specifically increased productive transcript levels in human cell lines and mouse brains.
- Treatment with the lead antisense oligonucleotide at postnatal day 2 or 14 led to reduced occurrences of seizures and sudden unexpected death in epilepsy (SUDEP).
- Increased levels of the productive transcript and Na1.1 protein were confirmed in the brains of treated mice.
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