Custom siRNA synthesis, priced by scale, purity and modification, and what to settle before you place an sirna order

Advertised prices, verified

What a custom siRNA order is priced on

1. Scale, in nanomoles of duplex. siRNA is quoted per synthesis at a nominal scale, and the delivered quantity of annealed duplex is what you should compare, not the scale of the individual strands. Screening work needs little material; a sustained knockdown campaign across many plates needs materially more and is priced in a different band.
2. Purification, which is not optional here. Unlike routine PCR primers, siRNA generally warrants HPLC purification. Truncated strands compete in the duplex and dilute the effective concentration, so a nominally identical order at lower purity delivers less real knockdown, which reads as biology rather than as a reagent problem.
3. Chemical modifications. 2'-O-methyl and phosphorothioate modifications improve nuclease stability and reduce off-target effects, and each is priced per modified position. For cell culture screening they are often unnecessary; for anything with a longer time course or an in vivo component they change the experiment enough to be worth the uplift.
4. Annealing and QC. Ask whether the quoted price includes annealing the two strands and confirming the duplex, or delivers single strands you anneal yourself. Both are sold, they are not the same product, and the difference is a common reason two siRNA quotes look far apart.

Controls are part of the order, not an afterthought

A knockdown experiment needs a non-targeting control synthesised to the same specification, at the same time, with the same purification. Ordering the control later or at a lower grade introduces a difference between arms that has nothing to do with the gene you are studying.

Budget for the control in the same purchase order. It is the cheapest way to make the result defensible, and it is the line most often cut when an order is trimmed.

Multiple sequences beat one good guess

Off-target effects are the standing criticism of any RNA interference result, and the standard answer is to show the same phenotype with two or more independent sequences against the same target. That means ordering several duplexes at screening scale rather than one at a large scale.

Price the order that way from the start: small-scale synthesis of three or four candidate sequences, then a larger order of whichever works. It is usually cheaper overall than committing scale to a sequence before you know it knocks down.

sirna vs aso, and which modality suits the target

A double stranded interfering RNA works through the cell's own slicing machinery in the cytoplasm and is the stronger choice for a cytoplasmic messenger. A single stranded antisense oligonucleotide works by several mechanisms and reaches places the RNA machinery does not, notably nuclear transcripts and splice junctions, which is why an exon skipping or a nuclear long non coding target belongs to it rather than to interference.

Chemistry and delivery follow from that. The antisense molecule is modified to survive and is taken up by many cell types without a carrier, while the interfering duplex needs a formulation or a conjugate. For a bench experiment, try both against the same target and read the knockdown and the toxicity together, because the cheaper reagent is not the cheaper experiment if it needs a carrier that kills the cells.

sirna delivery, and why it is the hard part

Synthesising a silencing duplex is routine; getting it inside a cell is not. A naked siRNA is large, charged and nuclease-sensitive, so delivery is either a transfection reagent in culture, electroporation for suspension and primary cells, or, in an animal, a lipid nanoparticle or a conjugate such as GalNAc that targets a receptor. Each brings its own toxicity and its own control: a non-targeting duplex delivered the same way, and a reagent-only well. Knockdown measured without those controls attributes the delivery method's effects to the sequence.

An hplc dad detector and the spectra it stores

An hplc dad records a spectrum at every point rather than one wavelength, which gives peak purity and identity confirmation beside quantitation, and that is what makes it the default detector for method development. The cost is slightly higher noise at a single wavelength, and the wavelength range and slit width are the specifications that decide spectral resolution.

An hplc fld and the sensitivity it buys

An hplc fld detects fluorescence, which is far more sensitive and selective than absorbance for compounds that fluoresce or can be derivatised, and it is what makes trace amino acid and mycotoxin methods possible. Excitation and emission wavelengths are part of the method, quenching by the mobile phase is real, and a non fluorescent impurity is invisible rather than absent.

custom oligonucleotide synthesis for modified RNA

For RNA, custom oligonucleotide synthesis adds the protecting group chemistry and the stability problem: yields are lower, purification is harder and the product needs ribonuclease free handling from the moment it arrives. Modification patterns for stability and for delivery are what most orders are really about, and the supplier's analytical package is what makes two prices comparable.

Common questions

What does custom siRNA synthesis cost?

It is quoted per synthesis at a stated scale, with purification and modification uplifts on top. The vendors in this index that publish figures are shown above with their own wording and the date we checked; compare on delivered duplex quantity rather than on strand scale.

Do I need HPLC purification for siRNA?

In most cases yes. Truncated failure strands compete in the duplex and reduce effective knockdown, and because the result still looks like biology rather than a reagent fault, under-purified siRNA is unusually expensive in wasted experiments.

Are chemical modifications worth the uplift?

For short cell-culture screens, often not. For longer time courses, serum-containing conditions and any in vivo work, 2'-O-methyl and phosphorothioate modifications improve stability and reduce off-target effects enough to change what the experiment can show.

How many sequences should I order per target?

At least two independent duplexes, ordered at screening scale. Showing the same phenotype with independent sequences is the standard defence against off-target artefacts, and it is cheaper to buy several small syntheses than to scale up the wrong one.

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