Custom siRNA & Dicer-Substrate siRNA
Engineered duplexes combining state-of-the-art RNAi chemistry with Dicer-substrate architecture for potent, durable, and specific gene knockdown.
Precision RNA Interference
Engineered for maximum knockdown efficiency
RNA Nanorobotics provides custom-synthesized small interfering RNAs (siRNAs) and extended 27-mer Dicer-substrate siRNAs (DsiRNAs) optimized for mammalian gene knockdown. By leveraging solid-phase synthesis on our MerMade 48x platform, we provide researchers with milligram-to-gram quantities of high-purity duplexes.
Dicer-substrate duplexes are designed to engage the endogenous RNAi processing machinery before RISC loading. This physiological entry route results in asymmetric strand selection, markedly higher potency, and extended duration of gene silencing compared to standard 21-mer oligonucleotides.
Duplex Formats & Applications
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Canonical 21-mer siRNA: Standard symmetric duplexes with 3′ dinucleotide overhangs for routine gene knockdown and high-throughput functional genomics screens.
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Dicer-Substrate 27-mer DsiRNA: Asymmetric duplexes featuring one 2-nt 3′ overhang and one blunt end that direct Dicer cleavage for enhanced RISC loading and ultra-low IC50 values.
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In Vivo Stable Duplexes: Heavy 2′-OMe/2′-F patterns combined with phosphorothioate internucleotide linkages for in vivo animal testing without carrier toxicity.
Technology Comparison
Standard 21-mer siRNA vs. Dicer-Substrate siRNA
| Feature | Standard 21-mer siRNA | Dicer-Substrate 27-mer (DsiRNA) |
|---|---|---|
| Length | 21 base pairs (symmetric 2-nt overhangs) | 27 base pairs (asymmetric 2-nt 3' overhang + blunt end) |
| Mechanism | Direct RISC loading (passive) | Active Dicer processing directly into RISC |
| Relative Potency | Standard nanomolar IC50 | Sub-nanomolar IC50 (10–100× higher potency) |
| Off-Target Effects | Moderate; dependent on seed region | Reduced off-target effects through directional Dicer loading |
| Serum Stability | Requires substantial 2′-modifications | Inherently higher stability enhanced with modified nucleotides |
| Recommended Scales | 50 nmol to 1 µmol | 50 nmol to 10 µmol (preclinical quantities available) |
Key Advantages
Why Choose Our RNAi Duplexes
Dicer-Substrate Architecture
27-mer duplexes designed to be processed directly by endogenous Dicer enzyme, facilitating efficient RISC loading and delivering up to 10–100× greater potency than conventional 21-mer siRNAs.
Stabilizing Chemical Modifications
Incorporate 2′-O-methyl, 2′-fluoro, phosphorothioate linkages, and inverted abasic end-caps to confer robust nuclease resistance in serum and eliminate immune activation.
Targeting Ligands & Labels
Functionalize with GalNAc, cholesterol, peptides, biotin, or fluorescent reporters (FAM, Cy3, Cy5) for cell-specific delivery and biodistribution tracking.
Validated Duplex QC
Every duplex is characterized by native and denaturing PAGE, ion-pair RP-HPLC, and electrospray mass spectrometry (ESI-MS) to guarantee stoichiometric duplex annealing.
Request Custom Duplexes
Order Custom siRNA or Dicer-Substrates
Provide your target accession number or sequence coordinates. Our computational biologists and synthesis team will design, optimize, and deliver high-purity duplexes.
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