%5d)
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Rugonersen sodium targets the UBE3A antisense transcript (UBE3A‑ATS), a long non‑coding RNA that silences the paternal UBE3A allele in neurons. In Angelman syndrome, the maternal UBE3A allele is mutated or deleted, while the paternal UBE3A allele is intact but silenced by UBE3A‑ATS. Rugonersen sodium is a locked nucleic acid (LNA)‑modified antisense oligonucleotide that binds to UBE3A‑ATS, leading to RNase H‑mediated degradation of the transcript. This unsilences the paternal UBE3A allele, restoring functional UBE3A protein production in neurons. This mechanism addresses the root cause of Angelman syndrome.
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| ln Vitro |
Rugonersen sodium is an LNA‑modified antisense oligonucleotide that reduces the silencing of UBE3A by targeting UBE3A‑ATS. In vitro, it unsilences UBE3A in human and cynomolgus monkey neurons. No specific IC50 or EC50 values are reported. The compound is designed to restore UBE3A protein levels, which is crucial for normal neuronal function, synaptic plasticity, and cognitive development. The locked nucleic acid (LNA) modification increases the stability, binding affinity, and resistance to nuclease degradation of the ASO.
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| ln Vivo |
Rugonersen sodium is under investigation in clinical trials for the treatment of Angelman syndrome. In preclinical studies, intrathecal administration of rugonersen in animal models (e.g., Ube3a maternal deficiency mice) has been shown to unsilence the paternal Ube3a allele, leading to the restoration of UBE3A protein in neurons and improvement in behavioral and electrophysiological phenotypes. Specific in vivo data (dosing, efficacy, behavioral tests) are not reported in the search results. In clinical trials (Phase 1/2), rugonersen is administered intrathecally (IT) via lumbar puncture to patients with Angelman syndrome. The primary endpoints are safety, tolerability, and pharmacokinetics; secondary endpoints include changes in EEG biomarkers, neurodevelopmental assessments, and UBE3A target engagement.
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| Enzyme Assay |
Rugonersen sodium is an antisense oligonucleotide (ASO), not an enzyme inhibitor. Its binding to UBE3A‑ATS is characterized by its melting temperature (Tm) and its ability to activate RNase H. The binding affinity is typically determined by hybridizing the ASO with a complementary RNA oligonucleotide and measuring the Tm by UV melting curve analysis. The purity and identity are confirmed by HPLC and mass spectrometry. The ASO sequence and chemistry are proprietary.
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| Cell Assay |
For in vitro cellular assays, human or cynomolgus monkey neurons (e.g., iPSC‑derived neurons, primary neurons) are seeded in 6‑ or 96‑well plates. Rugonersen sodium is added to the culture medium at concentrations of 0.1-1000 nM. For free uptake (gymnosis), cells are incubated with the ASO in serum‑containing medium for 3-7 days. For mechanistic studies, transfection reagents (e.g., Lipofectamine RNAiMAX) may be used. After 3-14 days of treatment, cells are harvested. UBE3A mRNA levels are quantified by qRT‑PCR, and UBE3A protein levels are measured by Western blot or ELISA. The unsilencing efficiency is expressed as the percentage increase in UBE3A protein levels compared to control. Off‑target effects are assessed by transcriptome analysis.
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| Animal Protocol |
For in vivo evaluation of rugonersen, Ube3a maternal deficiency mice (which lack maternal Ube3a and model Angelman syndrome) are used. Rugonersen sodium is administered by intrathecal (IT) or intracerebroventricular (ICV) injection at doses of 10-100 ug per mouse, typically once every 2-4 weeks for 1-3 months. At study endpoints, brains are collected, and UBE3A protein levels in different brain regions (hippocampus, cortex, cerebellum) are quantified by Western blot and immunohistochemistry. Cognitive and motor function is assessed using behavioral tests such as open field, rotarod, novel object recognition, and Morris water maze. EEG recordings are performed to measure brain activity and seizure‑like events. No specific protocols are provided.
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| ADME/Pharmacokinetics |
Rugonersen sodium (C204H235N63Na19O109P19S19, MW = 6948.00, purity ≥98%, CAS 2591588-58-6) is a white to off‑white solid powder. For storage, the powder should be kept at -20degC for up to 3 years, sealed and protected from light. For in vitro use, stock solutions in nuclease‑free water or PBS (1-10 mg/mL) can be prepared and stored at -80degC for 6 months or at -20degC for 1 month. For in vivo intrathecal administration, it is formulated in artificial cerebrospinal fluid (aCSF) or PBS. No detailed PK parameters (CSF half‑life, brain distribution) are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for rugonersen sodium are reported. As an investigational ASO, it is for research use only and is not intended for human use in its research grade. In preclinical studies, ASOs can cause neurotoxicity, hepatotoxicity, or immunogenicity at high doses. Standard laboratory safety precautions for handling oligonucleotides should be followed.
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| References | |
| Additional Infomation |
Rugonersen sodium is an investigational LNA‑modified antisense oligonucleotide for the treatment of Angelman syndrome (AS). AS is a rare genetic neurodevelopmental disorder caused by loss of function of the maternal UBE3A allele. There is currently no cure for AS. Rugonersen is designed to unsilence the intact paternal UBE3A allele, restoring functional UBE3A protein in neurons. The compound was developed by Roche and is being investigated in clinical trials (Phase 1/2). The LNA (locked nucleic acid) modification enhances target binding affinity, nuclease resistance, and CNS penetration. Rugonersen sodium is for research use only and has not received regulatory approval.
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| Molecular Formula |
C204H235N63NA19O109P19S19
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| Molecular Weight |
6948.00
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| CAS # |
2591588-58-6
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| Related CAS # |
Rugonersen; 2591587-57-2
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| Appearance |
White to off-white solid powder
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| SMILES |
[Rugonersen (sodium)]
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| Synonyms |
RG6091 sodium; RO7248824 sodium
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.1439 mL | 0.7196 mL | 1.4393 mL | |
| 5 mM | 0.0288 mL | 0.1439 mL | 0.2879 mL | |
| 10 mM | 0.0144 mL | 0.0720 mL | 0.1439 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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