Inspiration & validation
At the moment, the most well-known example of mRNA in the clinical setting is the use as vaccine against SARS-COV-2 (Corona virus). Before these vaccines, no mRNA medicine or vaccine had reached the market, mainly due to the mRNA technology being relatively new. Only recently, a combination of de-immunization of mRNA and improved mRNA-delivery technology, allowed effective use of mRNA.
These Corona vaccines have shown the robust immunological responses when expressing non-self proteins in a manner that mimics a viral infection (non-self proteins produced by autologous proteins). In addition, they proved that mRNA is a relatively easy technology to develop new vaccines with, because mRNA production is robust, regardless of sequence, whereas virus or protein production often require elaborate optimization and characterization.
We provide various researchers with mRNA coding for SARS-Cov-2 proteins, facilitating vaccine and knowledge development.
Novel therapies for rare metabolic disorders
Before development of the corona vaccines, several mRNA-based therapies were already in (clinical) development. Most of those were focused on rare metabolic disorders that affect young children and young adults. Here mRNA is employed to replace the missing enzyme(s) either in a emergency setting or in a repeated administration.
Most of these approaches progress steadily through clinical validation and show that with mRNA sufficient protein can be expressed in target organs (mostly the liver) to achieve clinically relevant decreases/increases in substrate or metabolites of interest. An important feat for these applications that repeated administration can be done without immunological rapid clearing of the nanoparticles.
RiboPro supports the development of at least 1 therapy for a rare disease with toxic build-up of metabolites involved.
With the success of the mRNA-based corona vaccines, various groups are now gearing-up to test the applicability to other corona proteins (variants of Spike protein, nucleocapsid proteins) and to other viral diseases. Popular targets include influenza, CMV and Zika. But also novel approaches against malaria and other infectious diseases are now being tried. RiboPro supports several research groups with high-quality mRNA coding for immunologically relevant proteins.
We see a trend that the lessons learned from the corona vaccines with respect to amount of protein to be expressed, expression kinetics, storage requirements of the vaccine, administration route, etc. provide another interesting route for vaccine innovation. Especially more stable formulations are in focus and provide solutions to vaccinate populations in warmer, more humid climates.
RiboPro's reporter mRNAs and investigational LNP formulations are currently being used for this work.
Immuno-oncology is often heralded as a revolution in cancer treatment. Growing or stimulating autologous/heterologous immune cells can be tricky, however. With mRNA, a precise dosing of the desired cytokine, growth-factor or (co-)stimulatory protein can easily be achieved. Contrary to DNA transfection or genome editing, mRNA can be much more precisely dosed, with a linear dose-expression curve over 5 orders of magnitude. Furthermore, mRNA provides a solution to unstable or hard-to-make recombinant proteins, by local production over several days with all the right post-translational modifications.
Exciting novel approaches could include in situ stimulation/expansion of the autologous immune-system or manipulating the tumor-micro-environment to become 'hot'.
RiboPro works together with several groups on various immuno-oncology approaches by supplying and optimizing mRNAs coding for specific cytokines/growth-factors.
Discovering the function of genes and rescuing knock-downs/knock-outs
mRNA is not only useful for therapy and vaccine development, but can accelerate your research as well. Because of the short time to protein expression, mRNA is suitable when time is of the essence. In addition, because mRNA is active in the cytoplasm and does not need to enter the cell, transfections are typically more successful than DNA transfections for hard-to-transfect and non-dividing cells.
Therefore, mRNA allows for transfections of freshly isolated (unculturable) primary cells, hard-to-transfect cell-types and even animals via systemic or local injection. And the best-part is that in most jurisdictions, mRNA transfection is not a GMO-activity, saving time and cost on containment and regulatory work.
RiboPro's mRNAs are frequently used for knock-down rescue experiments, as we can engineer siRNA/AON/miRNA sites out.
(trans)Differentiation of (stem)-cells and treatment of organoids
(trans)Differentiation of (stem)-cells often requires the expression of 1 or more transcription factors for a defined period of time. This is where mRNA shines; it can be engineered to have a well-defined half-life and can be re-applied as many times as needed to gain exquisite control over differentiation. Furthermore, mRNA is also well-suited to produce intra-cellularly active proteins, such as transcription factors.
Innovative and extremely robust options could include the engineering of differentiation-specific miRNA-sites in the mRNA, allowing auto-shut-off of the differentiation-inducing transcription factor once a particular differentiation checkpoint has been reached.
In addition to differentiation, mRNA is also very well suited to create induced pluripotent stem-cells from differentiated cells.
RiboPro supplies several groups with mRNAs coding for specific transcription factors.
Targeted therapy for CKD
Most diseases are primarily localized in a specific organ or cell-type. So also for Chronic Kidney Disease. Although the consequences can affect the entire body, CKD manifests primarily in the kidney, with a prominent role for the glomerulus (the filter of the kidney). From a toxicological and efficacy point of view, physically targeted mRNA treatment could dramatically improve patient outcomes.
When delivering mRNA with a nano-particle technology, surface modification is a proven method to alter the bio-distribution of the nano-particle. Customer Mercurna is currently developing a first-in-class glomerular targeted mRNA-treatment for Chronic Kidney Disease. Their peptide-based technology shows highly specific re-targeting to the glomerulus. Similar strategies with peptides, antibodies, Darpins, or other binding molecules, open up possibilities to target other organs and thus treat other diseases.
RiboPro works intimately together with Mercurna by supplying high-quality mRNA, advice and LNP-technology.
With an ageing population, chronic deteriorating diseases present an important social problem. This also includes bone decalcification, complicated breaks and general fragility. mRNA can provide a solution by a temporary expression of bone-healing, bone-forming or bone-fortifying proteins in a localized manner.
RiboPro works together with a research group developing new approaches for bone regeneration. We support our partners by supplying and optimizing mRNAs coding for specific cytokines/growth-factors, as well with advice on mRNA-delivery technology.
Get it while it is hot
Besides the many scientific advantages, mRNA have benefits for your career as well.
Due to the high visibility of the mRNA-based corona vaccines, mRNA has been in the public and scientific lime light. You may benefit from this, as we see a trend of increased funding availability for mRNA/gene therapy, funders sometimes reward the use of mRNA as a cutting-edge technology and publications on mRNA might score higher.
As a bonus, the public is already half-way educated on mRNA, enabling you to spread your findings to a broader audience.
At this moment, only a small percentage of scientists are using mRNA, thus it is very well possible that you are (among) the first in your field to use mRNA.
With mRNA you might be able to do things previously not possible or very difficult, or do things with more precision, yielding a clearer answer. This might allow you novel insights and break-through discoveries ahead of your competition. And let’s not forget the IP-options.
With limited funding and short tenures, it is imperative to get results fast. Cloning can be time-consuming and unpredictably frustrating at times. Covid-19 added extra pressure to that by limiting access to lab and now also certain materials.
mRNA can accelerate your research because there is not need for cloning, protein expression is fast and transfection is painless.