Rugonersen

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Rugonersen

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

2591587-57-2

RG6091
RO7248824

Rugonersen (RG6091; RO7248824) 是一种锁定核酸 (LNA) 修饰的反义寡核苷酸 (ASOs)，可减少泛素蛋白连接酶 E3A (UBE3A) 沉默。Angelman 综合征 (AS) 是一种由神经元 E3连接酶 UBE3A 缺失引起的严重神经发育障碍，Rugonersen 已用于 AS 的研究。

生物活性

Rugonersen (RG6091; RO7248824) is a locked-nucleic acid (LNA)- modifiedantisense 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 reasearch^[1]^[2].

IC₅₀& Target

ubiquitin-protein ligase E3A (UBE3A)^[1]

体外研究
(In Vitro)

RO7248824 (0-10 μM) show a nanomolar potency against UBE3A-ATS (EC₅₀=26.3 nM), UBE3A mRNA upregulation (EC₅₀=15.4 nM) and UBE3A protein upregulation (EC₅₀=24.8 nM) in Angelman syndrome (AS) neurons^[1].

体内研究
(In Vivo)

Rugonersen (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^[1].
Male cynomolgus monkeys^[1]Rugonersen (150 μg; i.c.v.; single dose) selectively and potently reduces UBE3A-ATS, while concomitantly upregulating the UBE3A mRNA and protein^[1].

Animal Model:	Male cynomolgus monkey^[1]
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)^[1]
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.

Clinical Trial

分子量

6530.00

CAS 号

2591587-57-2

Sequence

DNA, d(P-thio)((2′-O,4′-C-methylene)m5rU-(2′-O,4′-C-methylene)m5rU-(2′-O,4′-C-methylene)rA-C-(2′-O,4′-C-methylene)rA-C-T-T-A-A-T-T-A-T-A-C-T-(2′-O,4′-C-methylene)m5rU-(2′-O,4′-C-methylene)m5rC-(2′-O,4′-C-methylene)m5rC)

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.