| Size | Price | |
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| 1mg | ||
| Other Sizes |
| Targets |
Huntingtin (HTT) mRNA. Tominersen is a non-allele-specific antisense oligonucleotide that binds to HTT mRNA, leading to RNase H-mediated degradation of the transcript and subsequent reduction of both wild-type and mutant huntingtin protein (mHTT) production. This approach targets the root cause of Huntington's disease by lowering the levels of the toxic mutant protein in the central nervous system. The FITC-labeled version retains the same target specificity, allowing researchers to track ASO binding and internalization in cellular models without altering the antisense mechanism of action.
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| ln Vitro |
Dose-dependent reductions in mutant huntingtin protein concentrations have been observed in both human stem cell-derived neurons and HD mouse models following treatment with tominersen. In HD patient-derived fibroblasts, tominersen treatment leads to significant lowering of mHTT levels. The FITC conjugate retains antisense activity, enabling parallel assessment of target engagement and cellular uptake. Preclinical studies demonstrate that tominersen effectively inhibits HTT synthesis in various cell types, with potency consistent with second-generation ASO chemistry.
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| ln Vivo |
In mouse models of Huntington's disease, tominersen administration improves survival rates and reduces brain atrophy. Intrathecal administration in HD mouse models results in dose-dependent lowering of mHTT protein in cerebrospinal fluid and brain tissue, accompanied by improvement in behavioral and motor function deficits. The compound distributes throughout the central nervous system following intrathecal injection, achieving therapeutic concentrations in target brain regions. In non-human primate studies, similar mHTT lowering effects are observed, supporting translational relevance. The FITC-labeled version is primarily used for ex vivo tissue distribution analysis after in vivo dosing.
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| Enzyme Assay |
For non-cellular binding studies, surface plasmon resonance (SPR) or electrophoretic mobility shift assays (EMSA) can be used to assess direct hybridization of FITC-labeled tominersen to complementary HTT mRNA sequences. In a typical SPR assay, biotinylated HTT target RNA is immobilized on a sensor chip, and varying concentrations of FITC-labeled tominersen are flowed over the surface to measure binding affinity (KD). Alternatively, UV-visible spectroscopy at 260 nm and 495 nm can monitor duplex formation. For RNase H activity assays, labeled ASO and target RNA are incubated in cell-free systems containing recombinant RNase H, and cleavage products are analyzed by denaturing PAGE with fluorescence detection (excitation 495 nm, emission 520 nm).
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| Cell Assay |
For cellular uptake and activity studies, neurons (e.g., HD patient-derived iPSC neurons or primary cortical neurons) are seeded in 96-well plates and treated with FITC-labeled tominersen at concentrations ranging from 0.1-10 uM for 24-72 hours. Cellular uptake and localization are visualized by confocal laser-scanning microscopy (excitation 495 nm, emission 520 nm) or quantified by flow cytometry. Target engagement is assessed by collecting cell lysates and quantifying HTT protein levels via ELISA or Western blot, with normalization to housekeeping proteins. Co-localization studies with endosomal/lysosomal markers can elucidate intracellular trafficking pathways. Live-cell imaging may be performed to track real-time ASO internalization dynamics.
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| Animal Protocol |
Tominersen is administered via intrathecal injection directly into the cerebrospinal fluid to bypass the blood-brain barrier. In HD mouse models, a single intrathecal bolus injection (10-100 ug) is delivered via lumbar puncture or intracerebroventricular injection. For repeated dosing, animals receive injections every 4-8 weeks for up to 3-6 months. At study endpoints, CSF is collected via cisterna magna puncture, brain tissues (striatum, cortex, hippocampus) are harvested, and FITC fluorescence is measured in tissue homogenates or cryosections using fluorescence microscopy or plate reader. mHTT protein levels are quantified by ELISA or immunoassay, and pharmacokinetic parameters are derived from fluorescence intensity versus time profiles.
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| ADME/Pharmacokinetics |
Tominersen exhibits linear pharmacokinetics following intrathecal administration with dose-proportional increases in CSF exposure. A population PK model based on data from Phase I/II studies (doses 10-120 mg) describes rapid distribution within the CSF compartment, with peak concentrations observed shortly after injection. Tominersen is cleared from CSF with a terminal half-life of approximately 4-5 months, supporting quarterly or every-other-month dosing regimens. Systemic exposure (plasma) is minimal (<5% of CSF exposure) due to local CNS administration and limited transvascular efflux. Body weight and CSF volume are identified as covariates influencing PK. The FITC label does not significantly alter ASO pharmacokinetics, allowing labeled compound to serve as a tracer for unlabeled tominersen in co-dosing studies.
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| Toxicity/Toxicokinetics |
In Phase I/IIa clinical studies (NCT02519036), intrathecal tominersen was not accompanied by serious adverse events, with a safety profile comparable to placebo at Q16W 120 mg and at lower doses. However, the Phase III GENERATION HD1 trial (NCT03761849) was halted early in 2021 after an independent data monitoring committee found that the safety risks outweighed potential benefits in certain patient groups. Post hoc analysis suggested that younger individuals with less advanced disease might benefit from lower or less frequent dosing. No new safety issues have emerged in the ongoing GENERATION HD2 trial. Common adverse events include procedural complications from intrathecal injection and mild-to-moderate headaches. No serious drug-related toxicities have been reported in preclinical animal studies at therapeutic doses. The FITC label itself does not introduce additional toxicity beyond that of the parent ASO.
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| References |
[1]. Tabrizi SJ, et, al. Targeting Huntingtin Expression in Patients with Huntington's Disease. N Engl J Med. 2019 Jun 13;380(24):2307-2316.
[2]. Kordasiewicz HB, et al. Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis. Neuron. 2012 Jun 21;74(6):1031-44. |
| Additional Infomation |
FITC-labeled Tominersen is a research tool for studying ASO cellular uptake, intracellular trafficking, and tissue distribution. Tominersen (RG6042) was originally developed by Ionis Pharmaceuticals and Roche. Although the Phase III GENERATION HD1 trial did not meet its primary endpoints, the ongoing Phase II GENERATION HD2 (NCT05686551) continues to evaluate the safety, biomarkers, and efficacy of tominersen at lower doses (60 mg and 100 mg) in participants with prodromal and early manifest HD. As of 2025-2026, tominersen remains an investigational drug and has not received regulatory approval for the treatment of Huntington's disease. The FITC-labeled version is for research use only.
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| Molecular Weight |
7654.00
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| Appearance |
Typically exists as solid at room temperature
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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 and light. |
| 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 :≥ 100 mg/mL (~13.07 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.1307 mL | 0.6533 mL | 1.3065 mL | |
| 5 mM | 0.0261 mL | 0.1307 mL | 0.2613 mL | |
| 10 mM | 0.0131 mL | 0.0653 mL | 0.1307 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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