Leveraging the Power of mRNA: How Biotech Scale-up, RiboPro, Is Revolutionizing Therapeutic Development
Biotech scale-up RiboPro is putting the spotlight on important changes that must happen to leverage the power of mRNA for the development of therapeutics as well.
July 09, 2023 1:11 PM EDT | Source: Prodigy PR
Oss, Netherlands--(Newsfile Corp. - July 9, 2023) - The COVID-19 pandemic has been the litmus test for accelerated vaccine development in an effort to keep up with the overwhelming number of infections. The unexpected circumstances of this time allowed the nascent messenger RNA (mRNA) field to prove the potency, safety, but above all the drastically more efficient development trajectory achievable with this novel modality, causing many professionals to reimagine drug development practices. The lessons learned now translate into many ongoing trials on mRNA-based vaccines.
Within the realm of therapeutic drugs, Sander Van Asbeck had a similar moment of realization. After previously founding a company focused on developing targeted mRNA-based therapeutics, he wanted to create a company that could expedite and democratize the process of developing radically better therapies based on mRNA. Coupled with his extensive knowledge of molecular biology and drug delivery, Sander, Dr. Jürgen Dieker, and Prof. Dr. Roland Brock founded RiboPro in 2020.
Now a successful biotech scale-up, RiboPro was founded for the purpose of helping biotech and biopharma organizations design, test, produce, and scale mRNA vaccines and therapeutics effectively, with fewer barriers to their success. Since they started their one-stop-shop three years ago, the co-founders have discovered several aspects that are critical for the development of successful mRNA therapeutics, but less so for vaccines.
Because mRNA vaccines are intended to express foreign proteins usually close to the injection site with the goal to elicit an immune response for a short period of time, vaccines have some leeway when it comes to translational fidelity, targeting, residual immunostimulatory effects and stability. However, it is now becoming increasingly clear that for mRNA therapeutics, which typically require higher and repeated dosing, a highly localized therapeutic effect, and precise activity, these properties can and should be improved. This is why RiboPro has been developing over the past few years several complementary technologies that endow the mRNA therapeutics with a high level of fidelity, low immunogenicity and a lessened passive off-targeting.
Among the most important topics for developing highly-effective mRNA therapeutics is the challenge of evading the immune response to mRNA. Currently, the majority of drug developers believe that deimmunization of the mRNA is a solved issue, because of the good results obtained with the use of chemically modified nucleotides, such as N1-methyl-pseudoUridine. In reality, the effects of chemically modified nucleotides is not completely understood yet, and may have unintentional side effects in therapeutics.
The benefit of the chemically modified nucleotides relies on the reduced interaction of such nucleotides with specific RNA sensing receptors in the body. By preventing the mRNA from unintentionally activating these receptors, which are part of the antiviral response, the chemically modified nucleotides are preventing immune response related side effects and improving activity. However, other side effects may still occur because the protein translation machinery has difficulty decoding the mRNA, resulting in altered proteins with potentially toxic effects and even the induction of auto-immune disease. Since it is undesirable to, even temporarily, disable these defense mechanisms, RiboPro set out to find a solution for evading detection by the antiviral response. By exchanging canonical nucleotide triplets (codons) with synonymous ones within the mRNA strands, RiboPro's method specifically removes or reduces the affinity of those motifs within the mRNA strand that activate the immune response, hence they mRNA is de-immunized. The benefit of this method is correct translation.
RiboPro CEO Sander Van Asbeck describes why they emphasize the value of these alternative deimmunization protocols:
"We see at the moment a strong preference in the industry for the use of chemically modified nucleotides, especially for therapeutics. What we worry about is that we will discover the risks of these nucleotides the hard way in the upcoming years; when clinical trials involving large numbers of patients show relatively rare, but serious side-effects. Side-effects that will only surface at higher doses and prolonged use. In the worst-case scenario, you could discover that your drug is inducing autoimmune disease, which may persist beyond the duration of the trial or use of the medicine. While it's not yet confirmed this will happen, we see a significant risk based on our understanding of the underlying mechanisms. I think virtually the whole market is aware of the need for de-immunization of mRNA; however, I think there's an over-reliance on the knowledge obtained with specific chemically modified nucleotides in low-dose vaccines. Methods like ours may be more complicated, and may require more optimization to obtain the desired protein expression level, but we believe it is worth it in order to have better patient safety."
While learning how to create mRNAs that are better at immune escape, RiboPro has been exploring possible procedures for stabilizing their therapeutics. By having a more stable compound, drugs could be injected less frequently and patient satisfaction would be increased. RiboPro is currently researching how stability can be optimized without compromising the translatability of the mRNA nucleotide strands.
In addition to solving the problems related to mRNA itself, RiboPro also successfully mastered the art of active targeting. To reach the intended site in the body, mRNA is typically injected and travels via the bloodstream until it is taken up by a cell. Because mRNA is a sensitive molecule, the vast majority of mRNAs medicines use a delivery vehicle, protecting the mRNA on its journey to the active site within the body. Most frequently, so-called lipid nanoparticles (LNPs) are used as delivery vehicles due to their efficient endosomal escape.
When dealing with vaccines or secreted therapeutics, the exact cell that absorbs and translates the mRNA is less important than for therapeutics that need to function inside a specific cell. In the latter case, if the mRNA ends up in the wrong cell, this negatively impacts the therapeutic effect and might even cause side-effects. Currently, most LNPs have significant off-targeting towards the liver. As a solution, the delivery vehicles can be equipped with active targeting molecules, such as antibodies, that bind to the target cell and induce uptake of the nanoparticle and its mRNA cargo. By removing passive off-targeting properties from their delivery vehicles, RiboPro's lipid nanoparticles are much more likely to reach the desired target.
The company also has another cutting-edge project dedicated to building a machine that automates the production of mRNA drug substance and drug product.
"We are building a machine, with a roughly one square meter footprint, capable of producing very small amounts of mRNA, suitable for preclinical research, seamlessly scalable all the way up to kilogram-scale. Meaning that in that very same, single machine, we can accelerate drug discovery, supply clinical trials, and even could create enough vaccines for all 18 million people in the Netherlands, in case of a pandemic, in just a short weekend," says Sander Van Asbeck.
To stress the dedication towards this work, a quarter of RiboPro's team is focused on developing this solution that will be the only machine capable of seamless scaling production across several orders of magnitude, without requiring revalidation, speeding up drug development. Through its parallel cartridge design, the machine is also very well-suited for the manufacturing of personalized medicines. RiboPro expects to deliver a fully functioning beta-version, ready for first manufacturing assignments, within the next six months.
Overall, it is clear that the company is determined to empower drug developers, patients, and the entire medical field for creating more reliable, safe therapeutics.
Media Contact
Name: Lotte Tholen
Email: info@ribopro.eu
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Source: The Newsdesk
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