Gene Silencing
Potent & Specific Gene Knockdown by RNAi
Gene silencing with siRNAs is a powerful technique for studying gene function and regulating cellular pathways. By targeting specific mRNA sequences, siRNAs effectively reduce gene expression, enabling precise control in functional genomics, RNAi screening, and therapeutic research. Explore how siRNAs can streamline your gene silencing experiments.
siRNA pools (siPOOLs) are complex pools of 30 optimally designed siRNAs that have been shown to efficiently minimize off-target effects. Due to the picomolar concentration of each individual siRNA, off-target effects are reliably diluted. At the same time, the target gene is robustly silenced by the combined activity of many siRNAs (Hannus et al., 2014). The proprietary design algorithm guarantees the selection of potent siRNAs with maximum transcript coverage and avoids paralog target gene regions. siPOOLs thus generate reliable cellular effects, significantly improving specificity compared to individual siRNAs and low-complexity siRNA mixtures.
Advantages of siPOOLs:
- Defined pool of 30 selected siRNAs
- Extremely robust and efficient target gene silencing
- Maximum target gene specificity
- Use of the latest NCBI annotations of the human genome (RefSeq release 214)
- Uniformly efficient silencing of multiple target genes through siPOOL combinations
- Saves time and money by avoiding redundant experiments with multiple, non-specific single siRNAs
Main problem: off-target effects of siRNAs
Scientists have used RNA interference (RNAi) as a fast and efficient tool to study gene function. However, the off-target effects and variable performance of short interfering RNAs (siRNAs) remain a drawback that consumes valuable time and resources for validation efforts.

siRNAs generally bind to target RNA transcripts with full complementarity and lead to their degradation by the RNAi machinery. Off-target effects are largely caused by siRNAs that mimic endogenous gene regulators, microRNAs (miRNAs). Since miRNAs only require a 6-base-sead sequence with the 3'-untranslated region (UTR) to trigger downregulation of a transcript, siRNAs can thus alter the expression of numerous unintended targets.

Single siRNAs or siRNA pools of low complexity, containing 3 to 4 siRNAs, often hit multiple off-target genes and show variable target gene knockdown.
Short interfering RNA pools (siPOOLs) are highly complex and defined pools of 30 siRNAs, with each siRNA present at a picomolar working concentration.
This:
- Attenuates the off-target signature of each siRNA and increases on-target specificity.
- Ensures cooperative knockdown of the target gene, leading to more robust and reliable results.
Optimized and detailed siRNA design
With defined siRNA sequences within the siPOOL, targeting specific transcript isoforms or closely related genes can be optimized. Proprietary siRNA design algorithms select the most effective siRNAs based on thermodynamic properties that favor guide strand loading into the RNA-induced silencing complex (RISC) (see Technote 2 for more details on siPOOL design). Using the latest RefSeq annotations and genome-wide paralog filtering, siPOOLs are designed for maximum coverage of all target transcripts with high specificity.