| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Complement factor B (CFB)[1]
Complement factor B (CFB) mRNA. IONIS-FB-LRx is an antisense oligonucleotide (ASO) that binds specifically to complement factor B (CFB) mRNA. This binding recruits RNase H, which degrades the CFB mRNA, thereby reducing translation of complement factor B protein. By lowering factor B levels, the ASO inhibits the formation of the alternative pathway C3 convertase (C3bBb), blocking the amplification loop of the complement cascade. |
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| ln Vitro |
In vitro, IONIS-FB-LRx binds specifically to complement factor B (CFB) mRNA with high affinity. In cell-based assays using human hepatocytes (the primary site of CFB synthesis), treatment with IONIS-FB-LRx leads to a dose-dependent reduction in CFB mRNA levels and a corresponding decrease in secreted factor B protein. This results in reduced alternative pathway activity in conditioned media, as measured by AP-mediated hemolysis assays.
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| ln Vivo |
Every four weeks, IONIS-FB-Lrx is injected subcutaneously to target the hepatic expression of CFB[2].
In vivo, IONIS-FB-LRx effectively reduces circulating levels of complement factor B (CFB). In animal models, subcutaneous administration leads to a sustained reduction in CFB mRNA in the liver and decreased plasma factor B protein levels for several weeks. This results in a corresponding reduction in alternative pathway complement activity (as measured by AP50). In Phase 2 clinical studies, IONIS-FB-LRx reduced factor B levels and slowed the growth of geographic atrophy lesions in patients with AMD. |
| Enzyme Assay |
Binding specificity is assessed using a hybridization ELISA or surface plasmon resonance (SPR) with synthetic CFB mRNA target sequences. For in vitro potency, primary human hepatocytes are treated with serial dilutions of IONIS-FB-LRx (0.1-1000 nM) for 24-48 hours. CFB mRNA levels are quantified by qRT-PCR, and secreted factor B protein in the culture supernatant is measured by ELISA. The IC50 for mRNA knockdown is calculated.
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| Cell Assay |
For in vitro cellular assays, human hepatoma cell lines (e.g., HepG2) or primary human hepatocytes are seeded in 6-well plates and treated with IONIS-FB-LRx complexed with a transfection reagent (e.g., Lipofectamine 2000) at concentrations of 0.1-1000 nM for 24-48 hours. Cells are harvested for CFB mRNA quantification by qRT-PCR, and culture supernatants are collected for factor B protein measurement by ELISA. Cell viability is assessed by MTT assay to rule out cytotoxicity. Alternative pathway complement activity is measured using a rabbit erythrocyte hemolysis assay.
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| Animal Protocol |
The in vivo efficacy is evaluated in cynomolgus monkeys or human CFB transgenic mice. IONIS-FB-LRx is administered subcutaneously at doses of 1-30 mg/kg once weekly or once every 4 weeks. Blood samples are collected at baseline and at multiple time points (e.g., days 7, 14, 21, 28, 35, 42) to measure plasma factor B levels (by ELISA), alternative pathway complement activity (AP50), and classical pathway activity (CH50). Liver biopsies are taken to assess CFB mRNA knockdown by qRT-PCR. The duration of effect is typically 3-6 weeks after a single dose.
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| ADME/Pharmacokinetics |
IONIS-FB-LRx (sefaxersen) is an antisense oligonucleotide with a molecular weight of approximately 9056.30 g/mol. It is administered subcutaneously, which is the standard route for ASO therapeutics. The compound has a long half-life in plasma (days to weeks) due to its nuclease-resistant chemistry and high protein binding. In humans, subcutaneous administration results in sustained CFB knockdown for several weeks, supporting every-4-week dosing.
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| Toxicity/Toxicokinetics |
In clinical trials, IONIS-FB-LRx has been generally well-tolerated. The most common adverse events reported were mild-to-moderate injection site reactions (e.g., erythema, pain, swelling), headache, and arthralgia. As an ASO, there is a potential for thrombocytopenia and hepatotoxicity at high doses, though these were not dose-limiting. No significant increase in infection risk has been reported. Overall, the safety profile is favorable.
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| References | |
| Additional Infomation |
IONIS-FB-LRx (RG6299; sefaxersen) is an investigational antisense oligonucleotide developed by Ionis Pharmaceuticals and Roche. It has been investigated in Phase 2 clinical trials for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The program has been discontinued after Phase 2 due to lack of sufficient efficacy. It is not approved for therapeutic use and is available for research purposes to study factor B knockdown via ASO technology in complement-mediated diseases.
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| CAS # |
2272975-74-1
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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 |
| 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.) |
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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