Small interfering RNA (siRNA) silences specific genes by targeting complementary mRNA for degradation, making it a powerful tool in research and therapeutics for diseases such as cancer and genetic disorders, as well as in functional genomics to study gene function, pathway analysis, and large-scale screening experiments.

Synthesized as two complementary strands of RNA, siRNA often includes chemical modifications such as 2′-O-methyl groups or phosphorothioate backbones to increase stability, reduce off-target effects, and improve nuclease resistance. We use high purity methods and rigorous quality control to ensure the reliable performance of siRNA in various applications.

Length

We offer custom siRNA oligo synthesis, from 7 to 35 nucleotides, with options for chemical modifications followed by optimal purification steps to enhance stability and specificity for RNA interference applications.

Scales and Yields

The yield of oligo synthesis for siRNA is dependent on the purification method, synthesis scale, and modification complexity. Purification options like HPLC ensure the highest quality oligos, but this process will result in a reduced yield.

Please inquire if you have any specific requests on scale or yield.

Modifications

At Ella Biotech we provides a variety of oligo modification options for ASOs, enabling enhanced stability, specificity, and cellular uptake. Most of our standard modifications are also available for siRNA.

Please refer to the Modification Options for siRNA page for a list of the most commonly used modifications.

For specialized requirements, please contact us to discuss customized modifications that can enhance cellular delivery while optimizing siRNA performance in your research.

Backbone Modifications And Directionality

Backbone Modifications

siRNAs are often chemically modified to increase their stability and therapeutic efficacy. The following backbone and sugar modifications are available for our custom siRNA oligos:

Directionality

Regular phosphoramidite based oligo synthesis is done in 3′ -> 5′ direction. Change of synthesis direction offers additional functionality and enables synthetic pathways to modifications otherwise inaccessible. 

Please inquire if you need a modification that is not part of our standard offerings.

Purification

You can order siRNA with any of our available purification options. Please note that higher purification levels improve quality but will result in lower yield, especially for longer oligos. For optimal performance, we recommend HPLC purification, as it effectively removes sulfurization byproducts and ensures high-purity oligos.

For additional details, please refer to Purification Method in the Resources section.

If you require alternative purification options, please contact us.

Delivery Form and Packaging

We offer oligonucleotides in a variety of packaging formats, including single tubes, multi-well plates, as well as bulk options, in a range of concentrations, solutions, and aliquot options. Custom vial labeling is also available upon request.

* Possible concentration may depend on scale/yield, as low yields at high concentrations result in extremely small volumes that are very difficult to handle, e.g. 5 nmol at 5 mM would result in a volume of 1 µL.

Quality and Quality Control (QC)

For siRNA oligo synthesis, we ensure rigorous quality control through ESI-MS and HPLC to confirm purity and sequence integrity.
Each strand of duplex siRNA undergoes individual QC with ESI-MS and HPLC, followed by duplex QC with HPLC to verify accurate hybridization and product quality.

PTO is one of the most common modification options, where the introduction of non-bridging sulfur into the phosphodiester linkage improves nuclease resistance, biodistribution, and pharmacokinetics. However, this modification can create a chiral center that complicates quality control and purification.

Different conformations interact differently with RP-HPLC columns, causing the unified product peak to split into overlapping signals. As a result, broadened oligo peaks can interfere with n-1/n+1 species, reducing the effectiveness of RP-HPLC for purification and purity assessment.

To address these challenges while keeping screening oligo production cost-effective, we perform thorough QC via ESI-MS instead of analytical HPLC. This approach provides a comprehensive assessment of oligo quality and a clear visualization of impurity profiles. As a result, our QC criteria are primarily based on ESI-MS data, ensuring reliable analysis despite the complexities introduced by sulfur modification.

Additional Services

Production Time and Shipment

siRNA oligo production time varies with modification complexity, yield requirements, and order volume. Oligos with complex modifications take longer, and higher yields or larger orders may also extend production time.

The typical production time for siRNA oligo synthesis is 10 days (ranging from 7 to 15 working days) for each 96-well plate synthesis. Similarly, the production time for a 50 mg synthesis is also within the same time frame, averaging 10 days.

We use FedEx for both domestic and international shipments. For temperature-sensitive shipments, we offer either dry ice or blue ice (gel packs).