You need four things for each sequence: an Oligo ID/Name, the sequence written 5′ to 3′, the synthesis quantity (in nmol or µg), and any modifications or linkages required. You can send these in any format: email, Word, or Excel all work.

• Oligo ID / Name: a unique label for each sequence (e.g., "sgRNA-target-1"), which keeps multi-sequence orders organized.
• Sequence (5′ → 3′): standard single-letter nucleotide code.
• Synthesis quantity: in nanomoles (nmol) or micrograms (µg).
• Modifications & linkages: backbone chemistries (phosphorothioate, our proprietary PACE), sugar modifications (2′-OMe, 2′-F, LNA), functional labels (biotin, fluorophores), end modifications, or base analogs (pseudouridine, m6A). Full catalogue at cirena.com/rna-modifications.

Don't see what you need? Just ask. We like a challenge. Send orders or questions to sales@cirena.com and we'll respond within 24 hours.

Cirena synthesizes long RNA from 100–300 nucleotides as our current standard offering, though there's no hard floor or ceiling; every project is handled case by case. We're actively expanding our synthesis chemistry to consistently support lengths beyond 300 nt as part of ongoing R&D. If your project falls outside the standard range, reach out. We're happy to talk through your specific project and where our R&D capabilities currently stand.

No. Cirena will never offer crude or unpurified RNA; high purity is core to what we do. For early-stage screening or cost-sensitive applications where our standard purity level isn't necessary, we offer a lower-cost tier called Cirena Screening Purity. Reach out to rnatechsupport@cirena.com for details on what that tier includes and whether it fits your project.

Yes. Long guide RNA synthesis is one of Cirena's core applications, particularly for CRISPR and prime-editing systems, where guide length and site-specific modifications (including PACE near the 3′ end) affect editing efficiency and nuclease resistance. Contact sales@cirena.com to discuss guide design.

Not entirely. The two methods differ in how much site-specific control they allow. In vitro transcription (IVT) uses an RNA polymerase, typically T7, to assemble the strand from nucleotide building blocks; this works well for very long RNA (thousands of bases) at low cost, but the polymerase only accepts certain modified nucleotides, and whatever it accepts is incorporated at every position of that base. That's how modified mRNA is typically made: globally swapping in analogs like pseudouridine or N1-methylpseudouridine and adding features like 5′ caps and poly(A) tails. What it can't do is place a modification at one specific site.

Chemical synthesis builds one nucleotide at a time, which enables site-specific modifications and a much wider chemical toolkit, including most sugar and backbone modifications and precise labels that polymerases can't incorporate. More detail in our LinkedIn post comparing the two methods.

Chemical synthesis is the better choice when a project needs site-specific modifications (such as a PACE-modified guide RNA), a precisely defined 5′/3′ end without run-off transcription heterogeneity, or high sequence purity without the dsRNA byproducts that can trigger innate immune responses in cell-based assays. IVT is the better choice for very long RNA (thousands of bases, such as full mRNA) or large bulk quantities where uniform modification across the molecule is acceptable and cost-per-base is the priority. Most projects land clearly on one side once the modification and length requirements are specified.

Every order ships with a Certificate of Analysis that includes LC-MS and analytical HPLC data confirming sequence identity and purity.

LC-MS confirms sequence identity by measuring the molecular mass of the dominant species, and detects mass shifts indicating synthesis errors such as misincorporation, incomplete deprotection, or residual modification.

Analytical HPLC provides a purity profile (full-length product vs. truncated sequences and other impurities), reported as the area-percent of the full-length peak. For most long RNA research applications (CRISPR, prime editing, ncRNA), we recommend a minimum purity of ≥75% full-length.

At this length, high purity means full-length sequence integrity with minimal truncated species, strict removal of immunogenic dsRNA or abortive transcripts, and near-zero chemical adducts, not just a single percentage on an HPLC trace. This ensures the RNA is functionally homogeneous and ready for cellular or biochemical applications without background noise.

A minimum of ≥75% full-length purity is typical for CRISPR guide RNA, prime editing, and non-coding RNA research. Have a different application in mind? We're happy to walk through what purity target makes sense for your experiment; reach out to rnatechsupport@cirena.com.

This range sits in a gap between two established methods. Standard solid-phase chemical synthesis becomes increasingly inefficient as length grows, since each coupling step has a yield below 100% and overall yield drops sharply as more cycles are required, making high-purity synthesis above roughly 100 nt technically demanding. In vitro transcription handles thousands of bases easily but can't offer site-specific modifications or the same level of sequence control. Long RNA in the 100–300 nt range needs specialized chemistry to synthesize efficiently at high purity.

Shortmers are a normal consequence of the stepwise nature of solid-phase RNA synthesis, not a manufacturing defect. Each nucleotide is added through a chemical coupling reaction, and no coupling step is perfectly efficient.

When a coupling reaction is incomplete, some growing RNA chains fail to receive the next nucleotide. These unreacted chains are normally capped so they stop growing, creating truncated failure products. Because small inefficiencies can occur at every synthesis cycle, the number and variety of these products increase as RNA length increases.

Closely related impurities can also arise if an unsuccessful coupling isn't completely capped and synthesis resumes anyway, producing a sequence with an internal deletion. Other side reactions during synthesis or deprotection can generate additional product-related impurities.

The closest shortmers, particularly n−1 species, can be difficult to separate from full-length RNA because they differ by only a single nucleotide. This is one reason purification becomes increasingly important as chemically synthesized RNA gets longer.

For chemically synthesized long RNA, difficulty generally increases with length, since small amounts of incomplete coupling at each synthesis step can accumulate into shorter, closely related products. As the RNA gets longer, separating these products from the desired full-length RNA becomes increasingly challenging, because the closest failure products may differ from the intended RNA by only a single nucleotide.

Sequence composition adds another layer of difficulty. Highly self-complementary, G-rich, repetitive, or strongly structured RNAs may adopt multiple conformations or form aggregates that complicate purification and analytical characterization. Chemical modifications can also influence coupling efficiency, deprotection, solubility, or chromatographic behavior.

There's no single sequence feature that automatically makes an RNA unsuitable for synthesis. Manufacturability usually depends on the combination of sequence length, composition, structure, modifications, and desired purity. For particularly complex RNAs, synthesis and purification conditions can often be adjusted without changing the biologically required sequence.

There's no fixed length ceiling. Purity becomes the limiting factor well before synthesis becomes impossible, and how soon depends far more on purification technique and synthesis chemistry than on length alone.

Solid-phase RNA synthesis adds nucleotides one at a time, and each cycle has a finite coupling efficiency. Even small amounts of incomplete reaction accumulate over 100, 200, or more cycles, increasing the proportion and variety of truncated products in the crude material, a process shaped by the synthesis chemistry used, sequence composition, modifications, and deprotection conditions.

For the most common RNA synthesis chemistry (TBDMS), purity becomes limiting as sequences approach ~100 nt, due to cumulative n−1 shortmers and steric hindrance that reduces coupling efficiency. Published coupling-efficiency data extrapolate to roughly 27% crude purity for a 100-mer under standard TBDMS chemistry. Purification is also harder at this stage, since many of the failure products are chemically very similar to the desired full-length RNA, so the practical length limit depends as much on separating full-length product from closely related impurities at acceptable yield as it does on synthesizing it in the first place.

Cirena uses a proprietary synthesis chemistry developed at the University of Colorado, combined with optimized purification methods, to support high-purity RNA in the 200–300 nt range, enabling applications like long guide RNAs, structured non-coding RNAs, and emerging circular RNA constructs.

In practice, the "realistic" length for your project is determined by the purity your assay requires. For many research applications, purified long RNA performs equivalently to shorter oligos, provided failure sequences and protecting-group remnants are removed. If you're exploring a long or structured RNA design, Cirena can help assess feasibility and recommend a purification approach tailored to your sequence.

For chemically synthesized RNA, maintaining high product quality becomes progressively more challenging as length increases. Each nucleotide is added through a series of chemical reactions, and even small inefficiencies at individual synthesis steps can accumulate over a long sequence. Longer RNAs generally contain a larger proportion of shorter, closely related byproducts that must be removed during purification as a result.

There's not a single length at which RNA suddenly becomes difficult to manufacture. Sequence composition, secondary structure, chemical modifications, synthesis chemistry, and purification method can all influence the practical length limit, so two RNAs of the same length can differ substantially in synthesis yield and ease of purification.

With appropriate synthesis chemistry and purification, many RNAs in the 100–300 nt range can be produced at high purity for research applications. As sequences approach the upper end of this range, careful purification and analytical characterization become increasingly important for distinguishing the desired full-length RNA from closely related products.

Yes. Truncated sequences ("n−1" and shorter failure products) are not inert, and can measurably interfere with assays that depend on precise hybridization or structure. Because shortmers retain most of the parent sequence, they can still hybridize to complementary regions and compete with the full-length RNA.

In standard TBDMS synthesis, shortmers are the dominant impurity, and crude 100-mer purity can fall near 27%, meaning failure sequences may actually outnumber the full-length product before purification. Unpurified failure sequences are documented to interfere with hybridization, decrease enzyme activity, and lead to erroneous quantitative interpretation. A shortmer can bind a target sequence with similar affinity to the full-length RNA when the truncated region falls outside the primary recognition site, which reduces the effective concentration of the intended RNA in your reaction. In structured RNAs, even small deletions can shift secondary structure, creating off-pathway folds that compete with the native conformation.

Whether this matters for your specific experiment depends on how sensitive your assay is to hybridization competition or misfolding. With proper purification, these failure sequences are removed and long RNA behaves as expected. Cirena's workflow is designed to eliminate shortmers so your experiment reflects the biology of the full-length RNA, not the impurities.

Purification works because shortmers, while chemically similar to full-length RNA, still differ from it in length, charge, and structure, differences that high-resolution chromatographic methods (HPLC or anion-exchange) can exploit to reliably separate truncated species from full-length product, even when crude purity starts out low.

The n−1 species is the most demanding to resolve, since it differs from full-length RNA by only a single nucleotide, so achieving high purity is fundamentally a matter of accepting the right yield tradeoff. Even when full-length RNA starts out as the minority component of the crude mixture, high-resolution purification can still recover it at high purity.

Purification matters most for long or structured RNAs, where full-length purity has the biggest impact on downstream results. Removing failure sequences ensures the RNA in your experiment reflects the intended design rather than a mixture of truncated variants.

Cirena's proprietary synthesis chemistry and purification workflow is optimized specifically for long RNA (100–300 nt), where shortmer removal is most critical. By combining length-selective chromatography with sequence-appropriate conditions, Cirena consistently delivers high-purity RNA well beyond the typical ~100 nt limit of standard TBDMS chemistry. If you're planning a long or structured RNA and want to know what final purity is realistic for your sequence, reach out to rnatechsupport@cirena.com and we'll walk through it.

Modifications give you better control over what your RNA does, and doesn't do, once it's in your experiment, most commonly by improving stability against nuclease degradation.

Sugar modifications like 2′-OMe and 2′-F block endonuclease cleavage at specific sites, but the main protection comes from the backbone: modifications like phosphorothioate or phosphonoacetate (PACE) alter the linkages directly, extending functional lifetime and improving consistency across replicates, especially in longer or more complex designs.

Modifications also shape how RNA interacts with cellular machinery. Base analogs like pseudouridine or m5C can reduce immunostimulatory responses, which matters when you want RNA to be functional without triggering an innate immune reaction. Others, like biotin or fluorescent labels, add functional handles for detection, pull-down assays, or imaging.

Chemical synthesis can incorporate five general families of modification, each at a precise, site-specific position:

• Sugar modifications: improve nuclease resistance and binding affinity (2′-O-methyl, 2′-fluoro, LNA).
• Backbone modifications: guard against degradation and influence biological behavior (phosphorothioate, phosphonoacetate/PACE).
• Base modifications and analogs: reduce immunogenicity or fine-tune base-pairing (pseudouridine, 5-methylcytosine).
• Terminal modifications: support stability and downstream applications (5′ caps, specialized 3′ end groups).
• Functional labels and conjugates: biotin, fluorophores, amino or thiol linkers for detection, purification, and imaging.

Not sure what modifications fit your application? Contact rnatechsupport@cirena.com.

A phosphorothioate linkage replaces one of the non-bridging oxygens in the RNA backbone with a sulfur atom, and is one of the most widely used backbone modifications because it confers strong nuclease resistance while being relatively simple to synthesize. It's commonly used at the terminal few linkages of an oligo to protect against exonuclease degradation without modifying every position.

Both are sugar modifications made at the 2′ position of the ribose that improve nuclease resistance and binding affinity compared to unmodified RNA, but they trade off differently on immunogenicity. 2′-O-methyl (2′-OMe) occurs naturally and tends to reduce immunostimulation. 2′-fluoro (2′-F) offers strong binding affinity and nuclease resistance but is more prone to triggering innate immune responses when used extensively. The right choice depends on the balance of stability, binding affinity, and immunogenicity your application requires.

Not currently as a standard service, but it's an active area of R&D for us, and we're always interested in talking with researchers who have a capping strategy in mind. If 5′ capping is important for your project, reach out and let's discuss what's possible.

PACE (phosphonoacetate) is a backbone modification that replaces the standard phosphodiester linkage with a phosphonoacetate group: one of the phosphate's non-bridging oxygens is swapped for a small carboxymethyl arm. PACE linkages are highly resistant to nuclease degradation, preserve the native-like negative charge of natural RNA, and can improve cellular uptake, while layering cleanly alongside sugar and base modifications.

PACE is worth considering wherever durability matters most, for instance in CRISPR guide RNAs, where a few PACE linkages near the 3′ end help protect against degradation and can improve editing yields, or any application where the RNA needs to survive a demanding cellular environment. See more data on the PACE Modification page.

Both are backbone modifications that replace a non-bridging oxygen to confer nuclease resistance, but they differ in trade-offs. Phosphorothioate substitutes a sulfur atom and is widely used, well-characterized, inexpensive, and simple to synthesize, and it remains a reliable default when you don't need PACE's specific advantages. At high substitution levels, though, it can introduce slight duplex destabilization and some non-specific protein binding. PACE substitutes a carboxymethyl-bearing group instead; in Cirena's data it provides comparable or superior nuclease resistance while more closely preserving the native negative charge and duplex behavior of unmodified RNA. See the PACE Modification page for supporting data.

Yes. PACE is a backbone (linkage) modification, so it layers alongside sugar modifications (2′-OMe, 2′-F, LNA) and base modifications (pseudouridine, m5C) without conflict, since each targets a different part of the nucleotide.

Store lyophilized RNA at −20°C in a desiccated environment for a shelf life of up to 36 months; this is the form your RNA ships in and the most stable for long-term storage. Once resuspended, working aliquots are stable at 4°C for up to a month; avoid more than five freeze-thaw cycles.

• Use RNase-free tips, tubes, and gloves.
• Store in low-binding polypropylene tubes (e.g., Eppendorf LoBind®).
• Keep fluorescently labeled product away from light.
• Let the sealed tube reach room temperature (~5 minutes) before opening, to prevent condensation.

Let the sealed tube reach room temperature for about five minutes before opening, then resuspend in the buffer you plan to use in your experiment.

1. Let the sealed tube reach room temperature (~5 minutes) before opening.
2. Use the buffer you plan to use in your experiment.
3. Spin the tube for longer than one minute to fully dissolve the material.
4. Confirm concentration via UV measurement before use, since small deviations from the labeled concentration can affect experimental results.

Resuspend your RNA in your working buffer, which can be nuclease-free water or whatever buffer you're already using downstream in your experiment.

Cirena prices per order with a custom quote rather than a fixed price list. Pricing is tiered by quantity rather than scaling linearly with length, since our synthesis chemistry delivers high yields, more than enough for screening even at standard order sizes. Standard modifications don't carry an added cost; modifications that require purchasing new reagents or dedicated R&D time are quoted separately after a conversation with our team. The fastest way to get a quote: submit your sequences through our Order RNA tool, and you'll receive a quote within 24 hours.

Cirena has no minimum order quantities: order the amount you need for your experiment or screening, whether that's a small pilot quantity or a larger scale-up.

Yes, Cirena accepts institutional purchase orders. Onboarding timelines vary by institution, but we can typically get set up quickly with university and biotech procurement systems.

In addition to institutional purchase orders, Cirena accepts credit card payments, a good option if your lab or company prefers not to route through a PO.

Cirena ships both domestically and internationally. RNA always ships lyophilized, which avoids the complexity of cold-chain shipping and keeps your product stable in transit. For international orders, we work directly with you on customs documentation to keep the shipment moving smoothly.

Cirena only ships RNA that meets the purity specification stated for your order; product that doesn't meet spec doesn't go out the door. In the rare case an issue does come up, we proactively communicate with you directly to resolve it.

Turnaround for HPLC-purified orders under 30 nmol runs 12–25 business days depending on length, with longer and more heavily modified sequences taking more time:

These times run from order acceptance to shipment, so add transit time for your location when planning experiments. Longer sequences require more synthesis cycles and more demanding purification, and certain modifications can affect turnaround; we'll flag anything complex upfront. For quantities above 30 nmol, timelines vary, so reach out to sales@cirena.com and we'll work through the details.

Yes, rush and expedited orders are available for a small additional fee. Let our team know your deadline when you place your order, and we'll do everything we can to meet it.