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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Rovanersen targets the mutant huntingtin (HTT) mRNA, the transcript of the gene responsible for Huntington's disease. As an antisense oligonucleotide, it hybridizes to the target mRNA sequence through complementary base pairing, specifically binding to the mutated mRNA copy of the HTT gene. This binding recruits RNase H, which cleaves the RNA-DNA duplex, leading to degradation of the mutant HTT mRNA and reduced production of the defective huntingtin protein. The compound does not affect healthy HTT mRNA, preserving normal huntingtin function.
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| ln Vitro |
Rovanersen (WVE-120101) selectively cleaves the mutant huntingtin allele (mHTT) by RNase H in vitro in comparison to wtHTT without activating complement. In several cell lines, Rovanersen preferentially lowers the levels of mHTT mRNA and protein in comparison to wtHTT [1].
In vitro, Rovanersen specifically targets mutated mRNA copies of the HTT gene without affecting healthy mRNA. It prevents the production of faulty huntingtin protein by promoting the degradation of mutant HTT mRNA through an RNase H-mediated mechanism. The compound's specificity for mutant HTT mRNA over wild-type HTT mRNA is achieved through targeting single nucleotide polymorphisms or other sequence differences that distinguish the mutant allele. |
| ln Vivo |
In non-human primates (NHP), Rovanersen (WVE-120101) is present in the nuclear and perinuclear compartments of neurons in brain regions considered to be implicated in HD pathogenesis [1].
In vivo, Rovanersen has potential for treating Huntington's disease by reducing the levels of mutant huntingtin protein in the brain. Antisense oligonucleotides targeting HTT have been evaluated in preclinical and clinical studies for Huntington's disease. By specifically targeting the mutant allele, Rovanersen may reduce the toxic effects of mutant huntingtin while preserving normal huntingtin function. However, specific in vivo efficacy data for Rovanersen have not been detailed in the available literature. |
| Enzyme Assay |
For in vitro target engagement studies, cells expressing mutant and wild-type HTT mRNA are treated with Rovanersen at various concentrations (0.1-1000 nM). HTT mRNA levels are measured by RT-qPCR using allele-specific primers. Huntingtin protein levels are assessed by Western blotting or ELISA. The specificity of the oligonucleotide for mutant HTT mRNA over wild-type mRNA is determined by comparing the reduction in mRNA levels between the two alleles.
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| Cell Assay |
For cell-based assays, neurons or other relevant cell types expressing mutant HTT are treated with Rovanersen at concentrations ranging from 0.1-1000 nM for 24-72 hours. Cell viability is assessed, and huntingtin protein aggregation is evaluated by immunocytochemistry. Mutant HTT mRNA and protein levels are quantified by RT-qPCR and Western blotting, respectively. Off-target effects are assessed by measuring the expression of other genes.
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| Animal Protocol |
For in vivo studies, transgenic mouse models of Huntington's disease (such as the YAC128 or BACHD models) would be used. Rovanersen would be administered via intrathecal or intracerebroventricular injection. Huntingtin mRNA and protein levels in brain tissues would be measured. Behavioral assessments (motor function, cognitive tests) and neuropathological analysis (aggregate formation, neuronal loss) would be performed. However, specific in vivo protocols for Rovanersen have not been detailed.
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| ADME/Pharmacokinetics |
Rovanersen is an antisense oligonucleotide with a molecular weight of 6617. Storage is recommended at -20°C under nitrogen. The compound is for research use only and is not intended for human or veterinary use. Standard laboratory safety precautions should be followed when handling this compound.
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| Toxicity/Toxicokinetics |
As an antisense oligonucleotide, Rovanersen is expected to have a distinct pharmacokinetic profile typical of this class of molecules, including distribution to the central nervous system following intrathecal administration. Toxicological data for antisense oligonucleotides targeting HTT would be available from preclinical development programs. The compound is for research use only and is not approved for clinical use. Standard safety precautions should be followed.
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| References | |
| Additional Infomation |
Rovanersen (WVE-120101) is an antisense oligonucleotide that specifically targets mutated HTT mRNA copies without affecting healthy HTT mRNA, preventing the production of faulty huntingtin protein. It is being developed for Huntington's disease research. Rovanersen is a research compound and is not approved for clinical use.
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| CAS # |
2072901-32-5
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| Appearance |
White to off-white solid powder
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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 (e.g. under nitrogen), 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) |
H2O : ≥ 50 mg/mL (~7.56 mM)
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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.) |
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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