Therapeutic siRNA, Designed for

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Custom siRNA Synthesis

Potent, RNase‑resistant duplex siRNA tailored for gene silencing in cells and in vivo.

Overview

Small interfering RNA (siRNA) is a double‑stranded RNA duplex that guides RISC to a complementary mRNA for cleavage and degradation. Standard designs are 21‑mers with 2‑nt 3′ overhangs, while Dicer‑substrate siRNAs (25–27 nt) can improve potency via Dicer processing.

Bio‑Synthesis provides custom siRNA with stabilizing 2′‑modifications (2′‑OMe, 2′‑F, LNA), PS end‑caps, and advanced delivery conjugations. Each lot ships with rigorous QC and optional endotoxin and functional testing.

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At-a-Glance

  • Chemistries: PS DNA, 2′‑OMe, 2′‑MOE, 2′‑F, LNA (mixmer/gapmer), steric‑block (backbone‑modified)
  • Typical length: 12–30 nt (gapmers 14–20 nt; steric‑block 18–25 nt)
  • Purification: RP‑HPLC or IEX‑HPLC; PAGE optional
  • Conjugations: GalNAc clusters, cholesterol/lipids, CPPs/peptides, PEGs
  • QC: MS (ESI/MALDI), analytical HPLC, OD260; optional Tm and functional assays
  • Scales: 1 mg to gram quantities (RUO → GLP/cGMP on request)

Custom Synthesis Options

Parameter Options
Format 21‑mer (2‑nt 3′ overhang), 19‑mer blunt, 25–27 nt Dicer‑substrate; single strands on request
Strand Polarity Guide (antisense) & passenger (sense) annotated; 5′‑phosphate on guide available
Overhangs UU/dT‑dT default; custom bases or blocked overhangs available
Stabilization 2′‑OMe/2′‑F/LNA mix; PS end‑caps; terminal protections (inverted dT, Spacer C3)
Controls Scrambled, mismatch, and positive controls; 3–4 siRNA pools
Purification RP‑HPLC or IEX‑HPLC per strand; desalting for screens; PAGE on request
Annealing Delivered as annealed duplex (default); single‑strands optional
Delivery Format Lyophilized sodium salt; buffer/counter‑ion exchange available
QC Package MS (ESI/MALDI), analytical HPLC, OD260, duplex integrity; optional endotoxin (LAL)
Scale by Yield Desalted Invivo Invivo HPLC HPLC
10 nmole $165.00 n/a n/a n/a
25 nmole $270.00 $540.00 n/a n/a
50 nmole $320.00 $585.00 $825.00 $695.00
100 nmole $345.00 $625.00 $1,040.00 $880.00
150 nmole $385.00 $695.00 $1,205.00 $1,020.00
200 nmole $520.00 $790.00 $1,375.00 $1,165.00
300 nmole $580.00 $1,085.00 $1,680.00 $1,428.00
500 nmole $715.00 $1,050.00 $1,985.00 $1,685.00
750 nmole $790.00 $1,445.00 $2,450.00 $2,080.00
1000 nmole $11,850.00 $1,590.00 $2,825.00 $2,400.00
1500 nmole $1,320.00 $115.00 $3,115.00 $26,450.00
2500 nmole $1,980.00 $2,475.00 $4,365.00 $3,710.00
3750 nmole $2,205.00 $3,270.00 $4,950.00 $4,030.00
5000 nmole $2,895.00 $3,775.00 $5,650.00 $4,895.00
7500 nmole $3,225.00 $4,300.00 $6,250.00 $5,310.00
Contact us for order up to 1000 gram

Popular Modifications & Linkers

Category Examples Common Uses
2′ Sugar Mods 2′‑OMe, 2′‑F, 2′‑MOE; LNA (selected positions); UNA Stability, potency, reduce off‑target & immunostimulation
Backbone PS end‑caps (1–3 at termini), partial PS patterns Exonuclease resistance and PK tuning
Terminal / Protective 5′‑phosphate (guide), 3′‑inverted dT, Spacer C3/AEEA RISC loading, stability, spacing for conjugation
Fluorophores FAM, HEX, TAMRA, ROX, Cy3/Cy5, ATTO, Alexa Fluor Uptake/trafficking and imaging
Affinity Tags Biotin (TEG), Digoxigenin Pull‑down, capture, detection
Reactive Handles Amine, Thiol, Azide, Alkyne, DBCO/BCN, Maleimide Bioconjugation and click chemistry
Spacers / PEG AEEA, miniPEG, PEG(n), Ahx Solubility, PK tuning, steric relief

Delivery & Conjugations

Type Linker Chemistry Applications
GalNAc‑siRNA Triantennary GalNAc via amide/click linkers Hepatocyte targeting via ASGPR
Lipid‑siRNA Cholesterol, tocopherol, stearyl through heterobifunctional linkers Membrane interaction and uptake enhancement
Peptide‑siRNA (CPP/targeting) Maleimide–thiol, NHS‑amine, CuAAC/SPAAC Cellular uptake and tissue targeting
Antibody‑siRNA SMCC/maleimide–NHS, SPAAC, tetrazine‑TCO Targeted delivery and proximity assays
We offer much more than listed! - get in touch   

Quality Assurance

  • Mass spectrometry (ESI/MALDI) for each strand identity
  • Analytical HPLC for strand purity
  • Duplex integrity check (native HPLC/PAGE or thermal profile)
  • OD260 and concentration report
  • Optional: endotoxin (LAL), RNase testing, functional knockdown assays
  • Documentation: RUO by default; GLP/cGMP support on request

Typical Turnaround

Standard stabilized siRNAs: 2–3 weeks from order confirmation. Conjugated or heavily modified constructs may require additional time.

Lead time depends on sequence, modification density, and conjugation strategy; rush options may be available.

How to Order

  1. Share target gene/region, species, and desired format (21‑mer, Dicer‑substrate, blunt, pool).
  2. Select modifications and any conjugations.
  3. Choose scale, purification, and optional QC/functional tests.
  4. Receive a same‑day quote and timeline.

Need design support? Upload your target sequence and we’ll propose candidates with predicted Tm and seed off‑target review.

Design Checklist

  • Guide/passenger sequences and seed (positions 2–8) review
  • GC content ~30–55% and avoidance of long homopolymers
  • Overhang choice (UU/dT‑dT) and 5′‑P on guide
  • Sense‑strand deactivation and pool strategy (if needed)

Our Benefits

40+ Years of Proven Expertise

Decades of experience delivering precision, reliability and innovation.

Comprehensive Chemistry Portfolio

Extensive modification options tailored to your research demands.

High-Throughput Efficiency

Hundreds of sequences per order - consistently, accurately and fast.

From Discovery to Clinical

Full-spectrum support - from concept through clinical-grade productions.

What Are siRNA Oligos and Why They Matter

Short interfering RNAs (siRNAs) are essential tools for gene silencing in both research and therapeutic development. Synthesized as ~21 nucleotide duplexes, their efficacy depends heavily on thoughtful design and synthesis quality. Whether you're running a university lab or a biotech startup validating a new therapeutic target, the right siRNA oligos can determine the success of your experiment.

Why use custom siRNA?

  • Prescise Targeting: Reduced off-target effects with optimized sequence design
  • Efficient Delivery: using LNPs, GalNAc or other bioconjugation technology
  • Optimal chemical modifications for high safety profile for in vivo/in vitro use
  • Reproducibility: Batch consistency and quality control for reproducibility

Comprehensive siRNA Drug Delivery Solutions

End to End Services and Support

  • Complete Workflow: We support the full siRNA development cycle—from sequence design to synthesis, modification, and delivery.
  • Rigorous Testing: QC includes molecular weight, purity, cytotoxicity, and off-target screening.
  • Immuno-Safe Design: Formulations are optimized to minimize immune response.
  • Ongoing Support: Technical guidance and data-driven refinement help accelerate project timelines.

Specialize in Atypical Modifications

  • Backbone: Phosphorothioate, phosphoramidate modifications increase nuclease resistance.
  • Sugar Modifications: 2'-O-methyl, 2'-fluoro, LNA, BNA, ENA, tEC, FANA, UNA to enhance binding affinity and reduce immune stimulation.
  • Base Modifications: Unnatural bases modification to improve pairing specificity.
  • Terminal Modifications: 3' and 5' capping, cholesterol, lipid, PEG conjugation, siRNA-CPP Peptide conjugates aid in delivery and cellular uptake.

Formulation and Delivery

  • Formats: Duplex or triplex in lyophilized powder or ready-to-use solution.
  • Carriers: Delivery platforms include lipid nanoparticles (LNPs), dendrimers, and viral vectors for in vivo applications.
  • Client-Specific Needs: Delivery strategies should align with the target tissue, required efficiency, and stability demands.
  • Advanced Technologies: High-precision delivery is enabled by systems such as LNPs, GalNAc conjugation, and a range of non-viral carriers.
  • Therapeutic ReadinessAll formulations should be sterile, isotonic, and endotoxin-free to ensure safety and compatibility.

Quality Control and Validation

  • Core QC Tests: Each oligo batch undergoes analytical evaluation for purity, identity, appearance, quantitation, and impurities.
  • Optional Tests: Endotoxin levels, bioburden, sodium content, water content, and residual solvents can be assessed upon request.
  • Tailored to Grade & Application: QC methods are selected based on the intended use and required specifications.
  • Continus Support: Ongoing data analysis and solution refinement accelerate research and preclinical timelines.

siRNA Technology & Benefits

How siRNA works: Small interfering RNAs are double-stranded duplexes that enter the RNAi pathway. Dicer (for 25–27 nt substrates) processes the duplex and loads it into the RISC complex. The passenger strand is discarded; the guide (antisense) strand directs Argonaute-2 to complementary mRNA, which is cleaved and subsequently degraded, producing potent gene silencing.

Design Principles

  • Format: 21-mer with 2-nt 3′ overhangs (UU or dT-dT) or 25–27 nt Dicer-substrates for enhanced RISC loading.
  • Thermodynamic bias: Weaken 5′ end of guide to favor correct strand selection.
  • Seed optimization: 2–8 region screened to reduce off-targets; optional 2′-OMe in seed.
  • Base content: Target GC ≈ 30–55% and avoid long homopolymers or motif-based immunostimulators.

Stability & Specificity

  • 2′-modifications: 2′-OMe/2′-F/LNA patterns improve nuclease resistance and potency.
  • PS end-caps: 1–3 phosphorothioates at termini increase exonuclease resistance.
  • Sens/guide tuning: Sense deactivation and guide 5′-phosphate support efficient RISC loading.
  • Reduced immunostimulation: Strategic 2′-OMe substitutions mitigate TLR7/8 activation.

Benefits at a Glance

  • High potency: Robust knockdown with optimized 21-mer or Dicer-substrate designs.
  • Programmable specificity: Sequence-defined targeting with seed/off-target controls.
  • Enhanced durability: 2′-mods + PS end-caps for improved half-life in cells and in vivo.
  • Conjugation-ready: GalNAc for hepatocyte targeting, lipids/peptides for uptake, Ab conjugates for precision delivery.
  • Scalable & reproducible: Fully synthetic production from RUO to GLP/cGMP.

Need in vivo performance? We can combine GalNAc or lipid conjugation with tailored 2′-patterns and PS capping to balance potency, PK, and safety.

Use Case Why siRNA Helps Typical Setup
Cell-based gene knockdown Rapid, reversible target suppression 21-mer duplex, 2′-OMe seed, RP-HPLC; lipid transfection
In vivo liver targeting ASGPR-mediated uptake with durable knockdown GalNAc-siRNA with mixed 2′-OMe/2′-F and PS end-caps
Pooled screening Mitigates single-sequence off-targets 3–4 siRNA pool against one gene; desalting/HPLC by need
Imaging & trafficking Track uptake/localization Fluor-labeled sense strand with AEEA/PEG spacer

FAQ

Can siRNA be ordered in plates?

Yes, siRNAs can be ordered in plates.

For plate order inquiries, Contact us.

Duplex siRNA vs Triplex siRNA

Duplex siRNA: A sense and antisense strand with 2-nt 3′ overhangs. Standard for RISC loading and mRNA cleavage.

Triplex siRNA: Includes a third RNA strand using Hoogsteen interactions. Enhances specificity or introduces novel regulatory control.

Do I need to anneal siRNA?

No. siRNAs are delivered as duplexes and do not require annealing.

What length and overhangs are standard?

Most siRNAs are 21‑mers with 2‑nt 3′ overhangs (UU or dT‑dT). Dicer‑substrates (25–27 nt) can improve potency for some targets.

21mer vs. 27mer siRNA Design?

21mer siRNAs: Mimic Dicer products, bypass Dicer, and enter RISC directly.

27mer Dicer-substrate siRNAs: Require Dicer processing, improving RISC loading and gene knockdown efficiency.

What’s the ideal siRNA concentration for transfection?

Begin with 10–50 nM and optimize depending on the specific cell line and experiment.

27mer Dicer-substrate siRNAs: Require Dicer processing, improving RISC loading and gene knockdown efficiency.

Can I use siRNA in vivo?

Yes, though in vivo applications often require delivery vehicles such as lipid nanoparticles.

Do you deliver annealed duplexes?

Yes—annealed duplex is the default. Single strands can be supplied for in‑house annealing if preferred.

How can I reduce off‑target effects?

We recommend 2′‑OMe in the guide seed, strategic sense‑strand modification/deactivation, and optional pooling (3–4 siRNAs). We can advise during design.

Is immunostimulation a concern?

2′‑modifications (especially 2′‑OMe) help reduce TLR7/8 activation; avoiding certain sequence motifs also helps. Share your model system and we’ll tailor accordingly.

What is the best siRNA delivery method for cultured cells?

1. Lipid-Based Transfection (Most Common)
- High efficiency, easy protocol
- Best for most adherent and suspension cells
- Limitations: Can be toxic at high doses

2. Electroporation
- Ideal for hard-to-transfect cells like neurons and T cells
- Limitations: May cause cell death without optimization

3. Nucleofection
- Example: Lonza Nucleofector
- High efficiency for stem cells, neurons, and immune cells
- Limitations: Expensive and protocol-specific

4. Polymer-Based Reagents
- Example: PEI, JetPEI
- Cost-effective for scalable transfection
- Limitations: Lower efficiency, variable results

5. Viral Vectors (for shRNA, not siRNA)
- Suitable for long-term knockdown, not direct siRNA delivery.

How should siRNA be stored?

Store lyophilized siRNA at 4 °C (short‑term) or −20 °C (long‑term). In solution, use RNase‑free buffer, aliquot, and keep at −20 °C to minimize freeze‑thaw cycles.

siRNA Troubleshooting

Low Knockdown Efficiency: Verify sequence, concentration, and delivery method.

Precipitation: Ensure correct solvent use and avoid overheating.

Degradation: Use RNase-free techniques and storage solutions.

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Why Choose BioSynthesis

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