Compositions comprising elf4e inhibitors for diagnosis or treatment of disorders associated with increasing elf4e
A technology of composition and inhibitor, applied in the field of composition containing eIF4E inhibitor, capable of solving problems such as function weakening
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Embodiment 5
[0261] Treat FMCD epilepsy animal model with ASO
[0262] 5-1: Treatment of epilepsy by reduction of eIF4E expression in animal models (seizure monitoring)
[0263]It was observed that ASO#75 and ASO#77 of Table 2 constructed in Example 4-1 decreased eIF4E expression in animal models.
[0264] For this experiment, the animal model established using pCIG-mTOR p.C1483Y-IRES-EGFP and pCIG-mTORp.L2427P-IRES-EGFP of Example 1 was used, while pCIG-mTOR(WT)-IRES-EGFP(mTORp .C1483Y or mTOR p.L2427P) established animal model as a control. ASO was injected intracerebroventricularly (ICV injection) at a dose of 100-500 μg, respectively, into the brains of mice with established seizures. From the 3rd day to the 70th day after ASO injection, each mouse was recorded 12 h video 2-3 times a week for epilepsy monitoring.
[0265] According to the experimental results, it was found that the injection of ASO#75(ASO-1) or ASO#77(ASO-3) could significantly reduce the seizure frequency of the...
Embodiment 1
[0344] The mutant cells in the FMCD animal model of Example 1 were marked with GFP, and the GFP-positive cells were sorted by fluorescence-activated cell sorting (FACS) to obtain mTOR mutant cells.
[0345] Briefly, in mice electroporated in utero, cortical neurons expressing MTOR-WT, MTOR-p.Cys1483Tyr, or MTOR-p.Leu2427Pro, as well as a GFP reporter gene, were cultured in mice supplemented with 10 mM HEPES (Gibco, 15630-080) Dissected at E18.5 in Hank's Balanced Salt Solution (Life Technologies) with Pen / Strep (Life Technologies, 15140-122). To analyze protein expression regulation, the medium was supplemented with 100 μg / mL cycloheximide (Millipore, 239763), which is a ribosome elongation inhibitor.
[0346] To distinguish cells expressing the mutation, GFP-positive cortical fractions were identified from the electroporated area and cultured in Hibernate-E medium (Gibco, A12476) supplemented with GlutaMAX-I (Gibco, 35050-061) and B27 (Gibco, 17504-044). -01) were excised. ...
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