Realize your dream project with mRNA
made easy & affordable by the mRNA experts at RiboPro
HIGHEST QUALITY mRNA
No dsRNA, a high capping efficiency and a well-defined A-tail.
Receive your custom mRNA product within 2-3 weeks. We keep you updated all the way.
Our support team is here to help you with the entire process. From start to finish; we got you covered.
Start small at ng-scale and be sure we can support you to gram-scale. Always with constant quality.
If you are looking for a trust-worthy, experienced source of synthetic messenger RNA, you have come to the right address. We have more than 10 years of experience in mRNA synthesis and several years of experience in translating the needs of our customers into successful mRNA designs. RiboPro's custom mRNA synthesis provides transfection-ready mRNA for your experiments. We are able to provide you with as little as ng-scale for initial experiments, but also up to gram-scale for large projects. To be able to provide continuous service from bench-to-bedside, we are currently setting up GMP manufacturing and aim to be ready for orders in mid 2022.
In any case, the design, amount and other specifics will, of course, be based on your needs and preferences. Lengths up to 15k nt are possible and we offer many modification and purification options to match your experimental/medical requirements.
Tells us via our Quotation form exactly what you want and you will receive an initial quotation as soon as possible. In the form you can also add questions, remarks and ask our RiboProfessionals™ to contact you to help make adjustments to your mRNA-design/mRNA-project. Filling out the form is fast, easy and prepares our people to support you the best they can!
For a typical sequence, you will receive your order within 2-3 weeks. If you provide us with a suitable template, it may even be faster, because 3rd party de novo DNA synthesis is the most time-consuming step of our RNA synthesis process. Due to COVID-19 related busyness at our DNA suppliers, an additional week may be required from time to time.
Time is of the essence in science and drug development, and we work hard not to waste yours. So, we often start synthesis directly after your OK on the quotation, giving you some time to arrange the PO number internally. This ‘at-risk’ manufacturing is uniquely available at RiboPro. Re-ordering synthetic mRNA is also quick and easy; we keep the DNA from previous orders on file for an even quicker turn-around time.
RiboPro uses only canonical nucleotides, meaning that any sequence requested via the mRNAssembler™ PRO is unencumbered in terms of IP by our synthesis methods. If you requested our patent-pending sequence optimization method to de-immunize the mRNA, our terms and conditions allow you free use for non-commercial research & development. Licenses are available for commercial use.
When you ask RiboPro to make the best choices for your experiment, we always keep your budget in mind. We never recommend anything more than you need, and we never include any ‘fancy’ but meaningless options. You can trust us to get you the best custom synthetic mRNA for the best price. Another way we keep prices low, is through constant innovation and lean manufacturing methods.
RiboPro's patent-pending method to de-immunize mRNA is equivalent to or better than chemically modified nucleotides in preventing pro-inflammatory cytokines and enhancing protein expression.
Because we only use our own IP to create your mRNA and/or LNP-formulation, we can provide you with a clear and affordable route to the market and are happy to support your commercial ambitions.
We have 11 colors to fluorescently label any mRNA, including both your custom mRNA and our reporter mRNAs. Ideal as control, or for uptake and bio-distribution studies.
In addition to the synthesis of custom synthetic mRNA, we offer formulation services, RNAse testing and more to support your mRNA research.
for those who want RiboPro’s mRNA experts to make the hard choices.
Based on your experimental/medical needs, they will design the best (m)RNA for you. Including the selection of the best 5′ and 3’UTR, A-tail-length, capping type and capping method and more.
for those who have figured out exactly what they want.
We will synthesize exactly what you asked for. You may include your own 5′ and 3’UTR or choose any of our library. In addition, you have a wide range of modifications and purification options to choose from.
Once you send the form in, we take the following steps a.s.a.p. to help you get the best mRNA as fast as possible:
1. a RiboProfessional™ checks your request,
2. gets in touch if needed, and
3. sends you a quotation within 24h
4. when you OK the quotation, we get started.
For repeat orders (an option in our ordering menu), you will still get a quotation, but we often already start with synthesis ‘at risk’ from DNA that is ‘on file’ to realize the shortest possible turn-around time. Of course, you may still ask for amendments of the order based on the quotation. The risk is entirely ours.
During production, we do the following things:
For planning purposes, you will receive updates at steps 2, 4 and 6.
RiboPro's patent-pending sequence engineering method to de-immunize mRNA is equivalent to or better than chemically modified nucleotides in preventing pro-inflammatory cytokines and enhancing protein expression.
A successful mRNA experiment requires good transfection into your cell of choice. We can formulate any mRNA into our LNPs, to do exactly that. Our LNPs are highly efficient in mRNA delivery, low tox and can be easily post-modified.
We offer various mRNA-related contract research services, such as mRNA activity testing, mRNA uptake & bio-material release testing, as well as a whole host of other in vitro assays. Your mRNA never has to leave our facility for great results.
As supplier of synthetic mRNA, we know as no other how important it is to avoid RNAse contamination. But how to verify? With our RNAse-activity testing service, you will have peace of mind that your labware/solutions are clean.
Of course as a life-science researcher you have the knowledge and tools to produce any bio-molecule yourself. However, several issues make this difficult for (m)RNA.
So also for the synthesis of mRNA; the multi-step enzyme-based reaction, with 1 or more purifications, in addition to acquiring a suitable DNA template, can be time-consuming; taking 2-3 days per synthesis.
In addition, especially when a limited amount or number of mRNAs is required, the up-front cost for the reaction ingredients, the quality control, the certified RNAse-free buffers and consumables is high.
But perhaps more than the reasons listed above, very few labs are well-equipped to work with such a delicate molecule, which is subject to degradation to omni-present and hard-to-destroy RNAses. Working with mRNA as a final product in an experimental setting is certainly doable, but multi-step manipulations during synthesis in a sub-optimal environment present a significant risk to the integrity of the final product.
And finally, designing a high-performance mRNA requires very specific knowledge on 5’UTR and 3’UTR functioning, secondary structure formation of RNA, the induction of innate immunity by RNA, codon optimization, ideal A-tail length, etc.
By ordering your desired mRNA from RiboPro’s custom mRNA synthesis service you can get started with your experiment as quickly as possible, without hassle! No need to worry about RNAse contamination during production, no need to setup complex quality control, no need to invest in the equipment and materials; we take care of it all. Our RNA experts make sure you get the best results.
RiboPro’s custom mRNA service is very flexible; we include as much or as little as you need.
Generally speaking, we have 2 flavors:
A. You provide us with a (semi)suitable template, which we use as input for the RNA synthesis. Minor changes to the template to make it suitable are no problem for us.
B. You provide us with the desired sequence, and we perform de novo DNA synthesis to obtain a suitable template for the RNA synthesis.
So, in the full-service variant (B) the following is included:
1. mRNA design and optional sequence optimization
2. de novo DNA synthesis
3. DNA prep
4. RNA synthesis
5. RNA capping (up to 99% capped, and Cap1 modification possible)
6. A-tailing to desired length (up to 500nt)
7. 2 purification round
8. (optional) dsRNA removal procedure
9. Quality control (length, sequence verification (DNA), A-tail length, purity)
10. (optional) Aliquotation
11. Packaging & shipping
12. After-care to ensure success in your experiments
This very complete package is available from €660 + shipment cost (typ. €50-€150) + DNA synthesis (typ. €100-€200)
The performance of a messenger RNA, to be added to cells via standard transfection methods, greatly depends on the design of the sequence, the quality of the synthesis, chemical modifications of specific bases and the purity of the end-product. Introducing a sub-optimal mRNA into cells is known to trigger the innate immune response; resulting in lower protein expression, cellular toxicity and the release of pro-inflammatory cytokines.
For the best performance, we recommend the following combination of features to be selected for your custom mRNA:
• 5’UTR: no upstream ATG, kozak or similar present directly upstream of the start codon. For example RiboPro catalogue 5’UTRs.
• 3’UTR: selected from mRNAs known to be extra-ordinary stable.
• Cap1 – 95%.
• 120-150nt A-tail.
• dsRNA reduction.
These parameters will provide you with a decent expressing mRNA. However, for any of the following situations:
• therapeutic applications,
• a demand for high protein-expression,
• experiments incompatible with pro-inflammatory cytokine release,
• or any other application requiring the best protein expression and the lowest toxicity,
we recommend additional mRNA-specific sequence-optimization. Using RiboPro’s patent-pending technology allows for 5x more protein (as high as 40x more in specific applications) and significant reduction in pro-inflammatory cytokine production.
If you like to understand why these settings lead to the best performance, read more below.
Synthesizing a high-performance messenger RNA requires optimization all through-out the multi-step synthesis, including specialized purification.
First of all, during the enzymatic production process, dsRNA can be formed. dsRNA is one of the main triggers of innate immunity, primarily via TLR3 (endosomal recognition during transfection), OAS1, PKR and MDA5 (cytoplasmic sensors). RiboPro’s mRNA synthesis process results in the lowest amount of dsRNA possible. The method used to reduce the amount of dsRNA, also negatively affects the yield of ssRNA, so limited additional costs do apply compared to the standard method, because we increase the scale in order to obtain the guaranteed yield. Without dsRNA reduction, protein expression is typically 10-fold lower than with dsRNA reduction.
Secondly, currently no supplier can promise that 100% of all mRNA molecules will be capped. When uncapped, the 5’UTR of the mRNA contains a 5′ triphosphate, which can be a ligand for the cytoplasmic innate immune sensor RIG-I. RiboPro offers 2 capping grades (~80% and 95%+). If selecting the lower grade (cheaper), additional phosphatase treatment may be required to reduce RIG-I activation.
Third, if a cap is present, but no additional methylation of the first nucleotide (Cap0), then IFIT1 may be activated in certain cells, leading to around 30-50% reduction in activity in some experiments. This seems to be particularly relevant in cells of the immune system. RiboPro offers optional methylation of the first nucleotide (Cap1).
Finally, template DNA, salts and small RNA species (formed during abortive cycling of the RNA polymerase) must be carefully removed to avoid interfering with uptake and interpretation of results. RiboPro uses extensive DNAse I-based DNA removal, reducing the residual DNA to far less than 1 millionth of the RNA concentration.
Next to an optimized production process, RiboPro also has also developed a series of test for quality control, offering you peace of mind about the identity, purity and modification status of your order.
Do you have additional questions? Please contact us directly below or later via the contact page. We are happy to help!