Silencer Select siRNAs from Ambion
  • Incorporates the latest improvements in siRNA design, off-target effect prediction algorithms, and chemistry
  • Provides unrivalled silencing consistency, potency, and specificity
  • Yields cleaner, more consistent phenotypic data

The benefits of using Silencer Select siRNAs include:

  • Potent—up to 100-fold more potent than currently available siRNAs and fewer off-target effects
  • Most specific—Locked nucleic acid (LNA) chemical modifications reduce off-target effects by up to 90%
  • Reliable—demonstrated improvements in consistency and reliability of phenotypic results
  • Guaranteed—100% guaranteed to silence, the best guarantee in the industry

Interested in targeting long non-coding RNAs? Learn more about siRNAs targeting lncRNAs or search below for your lncRNA gene of interest.

Order your Silencer Select siRNA positive and negative controls

Targeted gene silencing with Silencer Select siRNAs

The Silencer Select design algorithm

  • Incorporates >90 different sequence and thermodynamic parameters
  • Increases predictive accuracy 28% over previous generation siRNA design algorithm
  • Yields siRNAs that are up to 100-fold more potent than both modified and unmodified siRNAs from other suppliers
  • Provides significantly higher percentage of “on-target” phenotypes compared to other siRNAs

Most siRNA design algorithms predict effective siRNAs that induce 70% target mRNA knockdown with only ~80% confidence and are inadequate for predicting more efficient siRNAs. Many RNAi applications demand better efficiency than current algorithms offer. Therefore, we used a powerful machine learning method and performance data from thousands of siRNAs to better understand the link between an siRNA’s sequence, target location, and thermodynamic properties and its silencing efficiency. The result is the Silencer Select siRNA design algorithm.

Silencer Select design algorithm significantly improves prediction of effective siRNAs

Figure 1. Silencer Select siRNA design algorithm significantly improves effective siRNA prediction accuracy. The Silencer Select siRNA design algorithm was used to design 155 siRNAs to 40 different targets. These siRNAs were tested side by side with siRNAs designed using the previous algorithm at 5 nM in HeLa cells. mRNA knockdown was measured 48 h post-transfection via qRT-PCR using TaqMan Gene Expression Assays. Results are expressed as percent of mRNA remaining compared to Silencer Negative Control #1 siRNA treated cells. The inset shows the percentage of siRNAs that elicited ≥70% and ≥80% mRNA knockdown.

Enhanced specificity to reduce off-target effects

Sequence-specific off-target effects are one of the primary reasons for false positive results in RNAi experiments. In addition to the potency improvements afforded by the Silencer Select algorithm and state-of-the-art bioinformatic filtering criteria, Silencer Select siRNAs incorporate novel modifications demonstrated to improve siRNA specificity.

The Chemical modifications in Silencer Select siRNAs:

  •  Consistently enhance guide strand bias, which has been shown to correlate strongly with knockdown efficiency
  • Prevent the passenger strand from inducing silencing, which serves to reduce off-target effects
    • Reduce the number of non-targeted, differentially expressed genes detected by gene expression array by up to 90% as compared to unmodified siRNAs
    • Do not negatively impact silencing efficiency and therefore do not compromise the expected on-target phenotypes
    • Yield cleaner, more consistent cell biology data
Silencer Select siRNA Modifications Reduce Off-target Effects and Yield More Reliable Phenotypic Data

Figure 2. Silencer Select siRNA modifications reduce off-target effects and yield more reliable phenotypic data. 53 different siRNAs, including older designs previously noted to elicit off-target phenotypes, were transfected into U2OS cells at 30 nM in both unmodified and Silencer Select modified formats. Mitosis and apoptosis were measured 48 hours later. Data is expressed relative to negative control siRNA transfected cells. Black = similar mitosis/apoptosis levels as control. Green = down-regulation. Red = up-regulation. Note that the expected mitosis and apoptosis phenotypes for PLK and WEE1 siRNAs are preserved with the modifications. In contrast the off-target apoptotic phenotypes elicited by 10 unmodified siRNAs were eliminated with addition of the Silencer Select modifications.

Silencer Select siRNA Modifications Reduce the Number of Differentially Expressed Off-Target Genes

Figure 3. Silencer Select siRNA modifications reduce the number of differentially expressed off-target genes. Three negative control siRNAs with and without the Silencer Select modifications were individually transfected in quadruplicate into HeLa cells at 30 nM. RNA was extracted and analyzed on an Affymetrix Human Genome U133 Plus 2.0 Array in triplicate. The y-axis indicates the average number of differentially expressed genes — those showing ≥2-fold change in expression versus mock transfected samples.

100 % Guarantee – The BEST in the Industry

At Thermo Fisher Scientific, we guarantee that when you purchase two Invitrogen Silencer Select Pre-designed siRNA to the same target, then those two siRNAs will silence the target mRNA by 70% or more. To qualify for the guarantee, siRNAs must have been transfected at ≥5 nM and mRNA levels detected 48h post transfection. Follow the link to learn more about our industry-leading guarantee.

Silencer Select Validated siRNAs

A subset of Invitrogen siRNAs to human targets have been functionally tested in-house and verified to reduce target mRNA levels by 70% or greater, enabling us to guarantee that these Silencer Select Validated siRNAs will knockdown their target genes. The data sheet provided with each of these siRNAs shows the extent of mRNA knockdown observed during testing and the exon targeted by the siRNA. For most types, full sequence information is also provided at no additional charge.

Open access to Silencer Select siRNA sequences and associated data

In recent years, siRNA screens have highlighted issues with the technology stemming from off-target effects, variable level of knockdown efficacy, and low-level confidence in hits from screening campaigns.

A genome-wide screen published in Nature by researchers at the National Institutes of Health highlights an effective approach to circumvent the challenges currently being faced by the screening community. New bioinformatics techniques to decipher real positives from false positives that arise from the seed region have been highlighted in this publication. Seed sequence-driven off-target effects have been extensively observed in siRNAs screens as they stem from the endogenous miRNA mechanism of seed-driven mRNA regulation. This seminal work highlights usage of high potency Silencer Select siRNA at lower siRNA concentration as arrayed singles allowing identification of off targets (false positive or false negative) stemming from the seed sequence. Such deconvolution is not possible for a pooled siRNA reagent approach where unique biology can be observed owing to two or more siRNAs working in a concerted manner.

The National Center for Advancing Translational Sciences (NCATS) and Thermo Fisher Scientific are providing all researchers access to siRNA sequences and associated data on PubChem from the human genome-wide Silencer Select siRNA library, which includes 65,000 siRNA sequences targeting more than 20,000 human genes.

Access the siRNA sequences deposited at the NCBI PubChem Substance Database by searching for a particular siRNA Assay ID.

Quality RNA synthesis

We synthesize and purify each siRNA in a state-of-the-art facility that is ISO13485 and ISO9001 certified to meet the highest quality standards. As part of our rigorous quality control procedures, each RNA oligonucleotide is analyzed by LCMS and/or analytical HPLC. The result is premium quality siRNA that is purified and ready to use.

Approximate turnaround times*

Standard purification 4 business days
HPLC purification 6 business days (20 and 40 nmol)
8 business days (160 nmol)
In Vivo ready 12 business days (100 and 250 nmol)
15 business days (1 µmol)
20 business days (10 µmol)
Cy3 and FAM labels 8 business days

*Estimated time from order confirmation to ship date from Pleasanton, CA for orders to be confirmed by 2pm PST. Does not include time required for shipping (typically overnight for US and Canada deliveries, 2 days for Europe, 2-3 days elsewhere).

The Silencer Select design algorithm

  • Incorporates >90 different sequence and thermodynamic parameters
  • Increases predictive accuracy 28% over previous generation siRNA design algorithm
  • Yields siRNAs that are up to 100-fold more potent than both modified and unmodified siRNAs from other suppliers
  • Provides significantly higher percentage of “on-target” phenotypes compared to other siRNAs

Most siRNA design algorithms predict effective siRNAs that induce 70% target mRNA knockdown with only ~80% confidence and are inadequate for predicting more efficient siRNAs. Many RNAi applications demand better efficiency than current algorithms offer. Therefore, we used a powerful machine learning method and performance data from thousands of siRNAs to better understand the link between an siRNA’s sequence, target location, and thermodynamic properties and its silencing efficiency. The result is the Silencer Select siRNA design algorithm.

Silencer Select design algorithm significantly improves prediction of effective siRNAs

Figure 1. Silencer Select siRNA design algorithm significantly improves effective siRNA prediction accuracy. The Silencer Select siRNA design algorithm was used to design 155 siRNAs to 40 different targets. These siRNAs were tested side by side with siRNAs designed using the previous algorithm at 5 nM in HeLa cells. mRNA knockdown was measured 48 h post-transfection via qRT-PCR using TaqMan Gene Expression Assays. Results are expressed as percent of mRNA remaining compared to Silencer Negative Control #1 siRNA treated cells. The inset shows the percentage of siRNAs that elicited ≥70% and ≥80% mRNA knockdown.

Enhanced specificity to reduce off-target effects

Sequence-specific off-target effects are one of the primary reasons for false positive results in RNAi experiments. In addition to the potency improvements afforded by the Silencer Select algorithm and state-of-the-art bioinformatic filtering criteria, Silencer Select siRNAs incorporate novel modifications demonstrated to improve siRNA specificity.

The Chemical modifications in Silencer Select siRNAs:

  •  Consistently enhance guide strand bias, which has been shown to correlate strongly with knockdown efficiency
  • Prevent the passenger strand from inducing silencing, which serves to reduce off-target effects
    • Reduce the number of non-targeted, differentially expressed genes detected by gene expression array by up to 90% as compared to unmodified siRNAs
    • Do not negatively impact silencing efficiency and therefore do not compromise the expected on-target phenotypes
    • Yield cleaner, more consistent cell biology data
Silencer Select siRNA Modifications Reduce Off-target Effects and Yield More Reliable Phenotypic Data

Figure 2. Silencer Select siRNA modifications reduce off-target effects and yield more reliable phenotypic data. 53 different siRNAs, including older designs previously noted to elicit off-target phenotypes, were transfected into U2OS cells at 30 nM in both unmodified and Silencer Select modified formats. Mitosis and apoptosis were measured 48 hours later. Data is expressed relative to negative control siRNA transfected cells. Black = similar mitosis/apoptosis levels as control. Green = down-regulation. Red = up-regulation. Note that the expected mitosis and apoptosis phenotypes for PLK and WEE1 siRNAs are preserved with the modifications. In contrast the off-target apoptotic phenotypes elicited by 10 unmodified siRNAs were eliminated with addition of the Silencer Select modifications.

Silencer Select siRNA Modifications Reduce the Number of Differentially Expressed Off-Target Genes

Figure 3. Silencer Select siRNA modifications reduce the number of differentially expressed off-target genes. Three negative control siRNAs with and without the Silencer Select modifications were individually transfected in quadruplicate into HeLa cells at 30 nM. RNA was extracted and analyzed on an Affymetrix Human Genome U133 Plus 2.0 Array in triplicate. The y-axis indicates the average number of differentially expressed genes — those showing ≥2-fold change in expression versus mock transfected samples.

100 % Guarantee – The BEST in the Industry

At Thermo Fisher Scientific, we guarantee that when you purchase two Invitrogen Silencer Select Pre-designed siRNA to the same target, then those two siRNAs will silence the target mRNA by 70% or more. To qualify for the guarantee, siRNAs must have been transfected at ≥5 nM and mRNA levels detected 48h post transfection. Follow the link to learn more about our industry-leading guarantee.

Silencer Select Validated siRNAs

A subset of Invitrogen siRNAs to human targets have been functionally tested in-house and verified to reduce target mRNA levels by 70% or greater, enabling us to guarantee that these Silencer Select Validated siRNAs will knockdown their target genes. The data sheet provided with each of these siRNAs shows the extent of mRNA knockdown observed during testing and the exon targeted by the siRNA. For most types, full sequence information is also provided at no additional charge.

Open access to Silencer Select siRNA sequences and associated data

In recent years, siRNA screens have highlighted issues with the technology stemming from off-target effects, variable level of knockdown efficacy, and low-level confidence in hits from screening campaigns.

A genome-wide screen published in Nature by researchers at the National Institutes of Health highlights an effective approach to circumvent the challenges currently being faced by the screening community. New bioinformatics techniques to decipher real positives from false positives that arise from the seed region have been highlighted in this publication. Seed sequence-driven off-target effects have been extensively observed in siRNAs screens as they stem from the endogenous miRNA mechanism of seed-driven mRNA regulation. This seminal work highlights usage of high potency Silencer Select siRNA at lower siRNA concentration as arrayed singles allowing identification of off targets (false positive or false negative) stemming from the seed sequence. Such deconvolution is not possible for a pooled siRNA reagent approach where unique biology can be observed owing to two or more siRNAs working in a concerted manner.

The National Center for Advancing Translational Sciences (NCATS) and Thermo Fisher Scientific are providing all researchers access to siRNA sequences and associated data on PubChem from the human genome-wide Silencer Select siRNA library, which includes 65,000 siRNA sequences targeting more than 20,000 human genes.

Access the siRNA sequences deposited at the NCBI PubChem Substance Database by searching for a particular siRNA Assay ID.

Quality RNA synthesis

We synthesize and purify each siRNA in a state-of-the-art facility that is ISO13485 and ISO9001 certified to meet the highest quality standards. As part of our rigorous quality control procedures, each RNA oligonucleotide is analyzed by LCMS and/or analytical HPLC. The result is premium quality siRNA that is purified and ready to use.

Approximate turnaround times*

Standard purification 4 business days
HPLC purification 6 business days (20 and 40 nmol)
8 business days (160 nmol)
In Vivo ready 12 business days (100 and 250 nmol)
15 business days (1 µmol)
20 business days (10 µmol)
Cy3 and FAM labels 8 business days

*Estimated time from order confirmation to ship date from Pleasanton, CA for orders to be confirmed by 2pm PST. Does not include time required for shipping (typically overnight for US and Canada deliveries, 2 days for Europe, 2-3 days elsewhere).

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Support

If you have any questions on products or ordering, please contact us at RNAiSupport@thermofisher.com

For questions on siRNA experiments or results contact a Technical Application Scientist at TechServices@thermofisher.com