Based on deep knowledge, we offer a suite of products and services that help innovators create the medicines of the future.
Our one-stop-shop has you covered on:
Optimal performance
The performance of an mRNA for research, vaccine or therapeutic use is critically dependent on several factors, including:
– the choice of therapeutic target (variant),
– the design of the sequence,
– (chemical) modifications,
– delivery vehicle composition, and
– targeting strategy
The combinatorial effects of these parameters can make selecting the most optimal composition challenging. Luckily, RIBOPRO has the experience and tools to help you design the best mRNA/product for your application.
RIBOPRO offers the design of your RNA product using proprietary algorithms to optimize sequences for various purposes.
These algorithms use a combination of:
1. our patented sequence-based de-immunization technology, ensuring optimal protein expression by avoiding ribosome inhibition as the consequence of TLR7/8 and TLR3 activation by the mRNA;
2. codon-optimization to improve protein expression in the target tissue based on the cell-type specific abundance of tRNAs, codon usage, and protein-folding kinetics; and
3. proprietary 5′ and 3’UTR libraries that can be combined to achieve the desired Ribosome-loading activity (5’UTR) and stability (3’UTR). Our UTRs are synthetic in origin and designed to add a minimum of weight to the product, maximizing the amount of gene product delivered per dose;
to generate an mRNA with the desired safety and expression profile.
Based on our patent-pending class of ionizable lipids, and novel core-lipid construct, we can design LNP-formulations for various types of applications. We have lipids available that are suitable for vaccination by delivering an adjuvating signal, as well as lipids with very low immunogenicity for therapy development.
However, we are not restricted to using our proprietary lipids. We also have extensive experience with formulating mRNA with commercially available lipids and experimental customer-generated lipids.
Working together with the targeting experts at mRNA drug-developer Mercurna, we offer tissue- or cell-specific targeting modifications of the LNP. A limited number of peptide-based targeting moieties is already available and via co-development novel targeting peptides may be developed. Non-peptide targeting ligands such as antibodies, DARPINs, glycans and others are also possible, because we have a variety of click chemistries available.
Beyond the design of your product, we use our extensive experience with literally hundreds of customer projects to help you get the most out of your studies through protocols, advice, and data interpretation.
We call that our success service, and it is included free-of-charge with any other product of service.
From R&D to GMP
Reproducibly producing high quality mRNA in sufficient amount is not easy and requires tight control over the process parameters, a stringent quality control, and the use of high quality raw materials.
RIBOPRO uses highly innovative, proprietary methods to synthesize high-quality, high-purity, full-length mRNA, with low levels of dsRNA, high capping efficiency, and well-defined poly(A)-tails, from either de novo or customer delivered DNA templates.
As a critical benefit for drug-developers, our process is highly scalable and GMP-ready. Read more on GMP services: RiboFluxTM
RIBOPRO has developed a proprietary system using in-house developed enzymes with enhanced stability, activity, and fidelity combined with progressively optimized, automated protocols to ensure efficient synthesis of pure, full-length mRNA.
These protocols allow for the production of short (around 100 nt) to extremely long (15k nt) RNA transcripts with minimum side-products and contaminants. Our (m)RNA products are suitable for the expression of small peptides and large proteins, the formation of circular RNA (circRNA), and as source of self-amplifying RNA (saRNA).
Any residual impurities are removed by our purification system, reducing such impurities at least 1000-fold.
To turn the basic RNA transcript into a fully functional mRNA, capping (addition of a 5′ cap) and A-tailing is required. Completeness of capping is not only required for full activity, but also to avoid innate immunity mediated by for example RIG-I.
We currently offer 2 methods of capping:
1. with our enzymatic Vaccinia capping system >99% capped mRNA can be achieved for typical, uncomplicated 5′ UTRs,
2. with our ARCA (Anti-reverse cap analog) or another cap analog based method complicated 5′ UTRs (with major or very stable secondary structure) can be capped co-transcriptionally. Of note, RIBOPRO has developed a proprietary method (ARCA-Active™) to ensure >95% capping with ARCA (100% correct orientation), where traditional protocols provide 50-80% capping via ARCA.
Of course, in case of customer preference, also uncomplicated 5′ UTRs can be capped using the co-transcriptional ARCA-based method.
For the addition of the poly(A)-tail, we offer currently 3 methods:
1. PCR-based addition to the DNA template as a rapid and robust method of ensuring >99% of RNA molecules carry an A-tail of sufficient length.
2. an enzymatic method producing a narrow distribution of fully-customizable A-tail lengths, and
3. a plasmid template-based method producing a highly defined A-tail length. Frequently requested lengths (120/150 nt) can be provided from stock templates.
Having high quality, well-defined poly(A)-tail ensure reliable expression over a defined period of time.
For research & development
Affordable & ready-to-use
Fantastic formulations
Any mRNA purchased from RiboPro can be formulated into a selection of nanoparticle technologies.
These technologies include:
– cationic peptides,
– cationic or ionizable polymers,
– cationic or ionizable lipids.
Our specialty is formulation in lipid nanoparticles (LNPs) of which we have several standard formulations, based on proprietary lipids, available that display high mRNA delivery efficiency with low toxicity and immunogenicity.
Our formulation services include:
– Producing nanoparticles of defined size
(80-250 nm, PDI <0.02)
– Buffer exchange (via dialysis)
– Dilution or concentration
(0.01-2 mg/mL mRNA, standard 1 mg/mL)
– Quality control (Size by DLS)
– Packaging and shipping
You may choose from various options:
Buffer
– Phosphate pH 6-8, standard pH 7.4
– Citrate pH 4-6
– MES pH 5.5-6.5
– HEPES pH 7-8
– Others upon request
Sterile filtering
– 0.22 μm (recommended)
– 0.45 μm
QC-assays:
– Zeta-potential by DLS
– Surface-charge by TNS
– RNA-encapsulation by RiboGreen
NB. We do not formulate mRNA obtained elsewhere.
mRNA focused
Not everyone has access to a lab or the time to do basic mRNA testing. Or, you may lack mRNA-specific knowledge or equipment. When ordering mRNA from RiboPro, you don’t have to have any of that; you have access to RiboPro’s CRO services. We offer a variety of standardized assays to assess the activity, toxicity and/or immunogenicity from your mRNA and/or LNP formulation.
This service is ideal for virtual biotechs and other that want to make rapid advances in the mRNA space.
All our CRO services are executed by experienced scientists and are serviced through our European site in the Netherlands.
RiboPro offers the following mRNA-focused (standard) CRO services:
– mRNA activity testing
– Protein expression profiling
– Immunological activation testing
– Toxicity testing (in vitro only)
– Release from bio-material testing
Other tests/assays may be available upon discussion. Contact our RiboProfessionals to learn what we can do for you!
Superior outcomes
Because RIBOPRO is a mission-driven company we care about your success, whether that is the succesful answer of a research question, or the development of a new medicine. Therefore, we are always available for advice, data-interpretation, and/or experiment/trial design, free-of-charge.
So, please do not hesitate to contact one of our Product Specialists to help you accomplish more.
“The high quality, stable and non-immunogenic mRNA generated by Ribopro is extremely suitable to meet our needs. The company also offers the qualified expert advice allowing the optimization of our experimental protocols.”
Prof. Dr. Elena Levtchenko
Professor at KU Leuven
“We have been ordering RNA from RiboPro, and find that they produce very good quantity product. Also, their customer service and technical support are excellent! Highly recommend this company.”
Albert Kwok
“RiboPro provided both the expert support and synthesized the high-quality mRNA to make our first gene manipulation experiments a resounding success. Furthermore, RiboPro was able to provide the mRNA constructs at an inordinate speed.”
Aviad Pato
Head of research at Gamida Cell
“Good service paired with quick delivery and competitive pricing. Quality of delivered material was also very good. I can recommend RiboPro as a supplier of mRNA material.”
Arturs Aksjonovs
“I really value the helpful contact with the Product Specialists that answered all my questions. This resulted in rapid and excellent service form RiboPro.”
Dr. Piter Bosma
PI at Amsterdam UMC