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Custom siRNA Synthesis

Custom siRNA synthesis services and siRNA oligo manufacturing for high-purity duplex siRNA, optimized gene silencing, and in vivo–ready conjugated siRNA.

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Custom siRNA Synthesis

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

Overview siRNA Benefits Synthesis Options Modifications Delivery & Conjugations QC How to Order Pricing FAQ Contact

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 up to 100 gram in 4–5 weeks. Each lot ships with rigorous QC and optional endotoxin and functional testing.

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At-a-Glance

  • Formats: 21-mer (2-nt 3′ overhang; dT/UU), 19-mer blunt, 25–27 nt Dicer-substrate, single-strands for custom duplexing)
  • Pools: 3–4 siRNA pools available
  • Purification: RP‑HPLC or IEX‑HPLC; PAGE optional
  • Stabilization: 2′-OMe/2′-F/LNA, PS end-caps, terminal protections
  • 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 siRNA Synthesis Options

Parameter Description Standard Offering Additional Notes
Format siRNA length & structure options 21-mer (2-nt 3′ overhang); 19-mer blunt 25–27 nt Dicer-substrate; single strands on request
Strand Polarity Guide/passenger orientation & modifications Guide (antisense) & passenger (sense) annotated 5′-phosphate on guide available
Overhangs 3′ overhang composition UU or dT-dT Custom bases or blocked overhangs available
Stabilization Chemical modifications for stability 2′-OMe/2′-F/LNA mix; PS end-caps Terminal protections (inverted dT, Spacer C3)
Controls Available control siRNAs Scrambled, mismatch, and positive controls 3–4 siRNA pools available
Purification Purification method per strand RP-HPLC or IEX-HPLC Desalting for screens; PAGE on request
Annealing Strand preparation & duplex assembly Delivered as annealed duplex (default) Single-strands optional
Delivery Format Physical format & formulation Lyophilized sodium salt Buffer/counter-ion exchange available
QC Package Quality control assays MS (ESI/MALDI), analytical HPLC, OD260, duplex integrity Optional endotoxin (LAL) testing

siRNA Pricing & Purification Grades

Pricing below is for single-strand siRNA up to 26 mer synthesized with 2′-Fluoro, 2′-O-methyl, and phosphorothioate (PS) linkages.

Additional per-base charges apply for longer siRNA and for extra modifications such as LNA, dyes, linkers, or conjugates. Prices are per strand; a standard siRNA duplex consists of two strands (guide and passenger).

Scale by Yield Desalted RNase-Free HPLC RNase-Free Dual HPLC In Vivo In Vivo RNase-Free HPLC In Vivo RNase-Free Dual HPLC
10 nmole$165.00n/an/an/an/an/a
25 nmole$220.00n/an/a$320.00n/an/a
50 nmole$265.00$410.00$505.00$365.00$495.00$745.00
100 nmole$305.00$495.00$590.00$405.00$580.00$830.00
150 nmole$345.00$570.00$680.00$445.00$655.00$905.00
250 nmole$405.00$655.00$780.00$505.00$740.00$990.00
300 nmole$595.00$875.00$1,025.00$695.00$960.00$1,210.00
500 nmole$795.00$1,075.00$1,240.00$895.00$1,175.00$1,375.00
750 nmole$890.00$1,290.00$1,485.00$1,040.00$1,390.00$1,640.00
1000 nmole$1,195.00$1,565.00$1,750.00$1,345.00$1,665.00$1,915.00
1500 nmole$1,420.00$1,815.00$2,060.00$1,570.00$1,915.00$2,165.00
2500 nmole$1,700.00$2,230.00$2,525.00$1,850.00$2,330.00$2,580.00
For gram-scale synthesis, GMP support, or chemistries not listed above, please contact us for a project-specific quotation.
Purification grades
  • Desalted: Basic desalting removes small-molecule impurities and salts but does not enrich for full-length product. Recommended for early screening and plate-based assays.
  • RNase-Free HPLC: Reverse-phase or ion-exchange HPLC under RNase-free conditions. Enriches for full-length siRNA and removes most shortmers; ideal for routine cell-based studies.
  • RNase-Free Dual HPLC: Two orthogonal HPLC steps (RP + IEX) using RNase-controlled workflow. Provides maximal purity (>90–95% full length, sequence-dependent) for sensitive assays or complex chemistries.
  • In Vivo Grade: Sterile, nuclease-controlled processing with defined endotoxin and bioburden limits. Suitable for pilot in vivo work and small-animal studies.
  • In Vivo RNase-Free HPLC: In vivo–grade manufacturing combined with high-resolution HPLC purification for low endotoxin and enriched full-length product—used for pharmacology and PK/PD studies.
  • In Vivo RNase-Free Dual HPLC: Highest research grade short of GMP. Dual purification plus stringent RNase/endotoxin control; ideal for critical in vivo experiments and IND-enabling studies.

Popular siRNA 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

siRNA Delivery & Conugations

We also offer advanced bioconjugation for siRNA via GalNAc, lipid, and antibody formats – see our bioconjugation services for more details.

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   
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siRNA 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 Custom siRNA

  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

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.

How should ASOs be stored?

Store lyophilized ASOs at 4 °C (short‑term) or −20 °C (long‑term). For solutions, use nuclease‑free buffer, aliquot, and keep at −20 °C to minimize freeze‑thaw cycles.

Do I need to anneal siRNA?

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

Can I use siRNA in vivo?

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

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.

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.

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.

Speak to a Scientist

Complete the form to receive a tailored quote. Your request will be emailed to info@biosyn.com and logged to your CRM endpoint (configure below).

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Recommended Reading on Custom siRNA and RNA Interference

Key publications supporting siRNA mechanism, design principles, and chemical stabilization strategies.

  • Fire A, et al. “Potent and specific genetic interference by double-stranded RNA in C. elegans.” Nature (1998).
  • Elbashir SM, et al. “Duplexes of 21-nucleotide RNAs mediate RNA interference in mammalian cell culture.” Nature (2001).
  • Czauderna F, et al. “Structural variations and stabilizing modifications of synthetic siRNAs in mammalian cells.” Nucleic Acids Research (2003).
  • Allerson CR, et al. “Fully 2′-modified oligonucleotide duplexes with improved in vitro potency and stability.” J Med Chem (2005).
  • Krützfeldt J, et al. “Silencing of microRNAs in vivo with ‘antagomirs’.” Nature (2005).
  • Prakash TP, Bhat B. “2′-Modified oligonucleotides for antisense therapeutics.” Curr Top Med Chem (2007).
  • Nair JK, et al. “Multivalent N-acetylgalactosamine–conjugated siRNA for targeted delivery to hepatocytes.” J Am Chem Soc (2014).

Why Choose Bio-Synthesis

Trusted by biotech leaders worldwide for over 40+ years of delivering high quality, fast and scalable synthetic biology solutions.

Greetings Researchers,

Please be advised that any information, guidelines, writeups, and oral/video/graphic content on our website are intended solely as general guidelines.
It is the researcher's sole responsibility to conduct thorough research on the designs of the products intended for their experiments before submitting
their designs to Biosynthesis for review of production feasibility.
Thank you for your understanding.

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