Rugonersen (C007B-415564)

Rugonersen (RG6091; RO7248824) is a locked-nucleic acid (LNA)- modified antisense oligonucleotides (ASOs), and results in reduction of ubiquitin-protein ligase E3A (UBE3A) silencing. Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of neuronal E3 ligase UBE3A, Rugonersen has been used for AS reasearchIn VitroRO7248824 (0-10 μM) show a nanomolar potency against UBE3A-ATS (EC 50 =26.3 nM), UBE3A mRNA upregulation (EC 50 =15.4 nM) and UBE3A protein upregulation (EC 50 =24.8 nM) in Angelman syndrome (AS) neurons. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoRugonersen (RO7248824) (24 mg/monkey; i.t.; for 8-85 d) is well tolerated without adverse in-life effects or tissue pathology and produced a robust, long lasting (up to 3 months) paternal reactivation of UBE3A mRNA/protein across key monkey brain regions . Male cynomolgus monkeys Rugonersen (150 μg; i.c.v.; single dose) selectively and potently reduces UBE3A-ATS, while concomitantly upregulating the UBE3A mRNA and protein . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male cynomolgus monkey Dosage: 24 mg per monkey Administration: Intrathecal injection; single dose or twice dose with 2 weeks apart; sacrificed at 8, 15, 29, 57, and 85 days after the last dose Result: Resulted a long duration of action on paternal UBE3A reactivation in NHP brains after IT delivery. Animal Model: WT and AS Ube3a m- / p+ mice adult mice (10-12 weeks old) Dosage: 150 μg per mice Administration: Intracerebroventricular injection; single dose; harvested at 2 weeks post injection Result: Revealed a steep relationship between UBE3A-ATS knock-down and UBE3A mRNA/protein upregulation, whereby an almost 90% downregulation was needed to achieve a 50% upregulation, respectively.Form:SolidIC50& Target:ubiquitin-protein ligase E3A (UBE3A). Molecular Weight: 6530.3