The Future of mRNA Therapies

دقائق

4 Aug, 2025

Aurelie Demont

Messenger ribonucleic acid (mRNA) technology has come of age in the last few years and is set to transform a vast range of biomedical applications.

This technology had been in development for decades, but it gained global prominence during the COVID-19 pandemic when it was used as the basis for urgently needed vaccines. The development of mRNA therapies still encounters various technological and production challenges that hinder its progress toward widespread adoption. However, recent advancements have positioned this technology to significantly impact vital therapeutic areas in the biomedical sector, including oncology, immunology, genetic disorders, and infectious and chronic diseases. The emergence of mRNA therapies has been facilitated in part by simultaneous advances in precision instrumentation and measurement technologies. While vaccines will likely remain a central application of mRNA technology, other applications, such as gene editing and protein replacement, are likely to have equally transformative effects. This article focuses on the improvements in the efficiency of mRNA therapy development and how this will allow mRNA technologies to reach their potential as game-changing therapies for a range of conditions.

"METTLER TOLEDO's analytical instruments facilitate accurate measurement of key parameters such as purity and concentration, crucial for optimizing yield and ensuring product integrity in mRNA therapeutics.”
Dr. Hans-Joachim Muhr, Segment Business Development Manager

mRNA technologies have seen rapid advances in recent years. This is primarily due to the successful overcoming of major production barriers and logistical challenges related to their real-world storage, distribution, and implementation.

Stability

mRNA is an inherently unstable molecule that is highly temperature sensitive and prone to spontaneous autohydrolysis. This has implications for its durability during transport, storage, and therapeutic application. mRNA must be stored at very low temperatures to remain stable, but it can degrade over time, even in optimal conditions.

Immunogenicity

Exogenous RNA is immunogenic, which means that mRNA therapies can cause severe immune reactions that exceed the required response to the target antigen and present a significant obstacle to their implementation in humans. Modifying uridine bases and designing sequences to reduce the abundance of double-stranded RNA helps to reduce unwanted immunogenicity but it remains an important issue that future formulations must address. Residual DNA used in the production of mRNA therapies can significantly contribute to unwanted immune responses in recipients if not adequately removed from formulations.

Translational Efficiency

mRNA therapies must be translated using endogenous translation machinery to have their therapeutic effect. However, early iterations of mRNA therapies suffered from inefficient rates of translation, which reduced the effective therapeutic dosage.

Production bottlenecks

Large-scale production of mRNA is constrained by reagent costs and complex technical processes. A particularly costly step is RNA capping, which requires a large quantity of expensive reagents. Early reagents used for capping also had low capping efficiency and had a chance to yield untranslatable mRNA molecules

Advancements Since the Covid Vaccine

mRNA Formats

mRNA molecules are now produced in various formats, including circular RNA and self-amplifying RNA. These formats help to overcome issues with stability, immunogenicity, and dosage. Improvements in codon optimization have helped with translational efficiency and structural stability issues.

Production Innovations

The emergence of new capping reagents has removed a significant bottleneck in large-scale mRNA production. Furthermore, general improvements in laboratory automation, storage, weighing, and analytical instrumentation contribute significantly to faster development cycles. Innovations have also enabled specific processes that previously required separate reactions to be completed in a single production step. For instance, in vitro transcription and capping can now be carried out in the same mixture, simplifying the production workflows.

Delivery Systems

Rapid advances have been made in mRNA delivery systems, particularly in lipid nanoparticles (LNPs). LNP delivery systems help maintain mRNA stability during delivery and reduce immunogenicity.

METTLER TOLEDO provides automated platforms for in-vitro mRNA transcription that help to reduce costs and eliminate common contaminants. It also offers reliable solutions for producing PEG-lipids used in LNPs and provides UV/Vis spectrophotometry tools for quality control throughout mRNA therapy development.

Accelerated Design

Artificial intelligence (AI) is becoming increasingly important in helping automate mRNA vaccine design, accelerating the development process by optimizing the selection of effective and stable mRNA sequences. For example, one AI tool enabled the development of a COVID vaccine with a longer shelf life that elicited a larger immune response compared to previous design methods. AI could also be used to optimize sequences for other applications beyond mRNA vaccines.

Advanced Precision Technology and Automation

The development of mRNA therapies occurs in an environment that is both highly competitive and time-sensitive, making advancements in analytical laboratory tools crucial for success. Modern precision technologies help to ensure accuracy and speed in developing these cutting-edge technologies, reducing time-to-market, and helping companies align with industry and regulatory standards. METTLER TOLEDO offers automated reactor control systems, including those for in-vitro mRNA transcription, that greatly enhance the efficiency of developing mRNA therapies. These systems reduce variability, ensuring reproducibility and scalability in the development process.

Accelerated Preclinical Testing

Automation is revolutionizing workflow efficiency and accuracy across the life science sector. It is particularly impactful in automating high-throughput assays, including cell-based approaches. Cell-based assays serve as the foundation for testing various parameters of mRNA vaccines during their development. This includes testing mRNA constructs for antigen production, immunogenicity of the antigen, and cellular toxicity. Toxicity testing is critical for developing any new therapy but is particularly important for understanding the impact of new formulations and delivery strategies for mRNA therapies.

Accelerated Clinical Testing

Many mRNA vaccines designed during the COVID pandemic were scheduled for accelerated approval; however, technological improvements have also enabled accelerated clinical testing of these models. AI is helping to streamline clinical trial design and execution by allowing the selection of more appropriate cohorts, optimizing patient recruitment, and enhancing data analysis to identify patterns and outcomes more accurately. Advances in analytical instrumentation continue to improve production workflows, including the precise weighing of reagents and analytical tests, including mass spectroscopy, which is used to validate the quality of mRNA technologies. These improvements help researchers align with regulatory requirements and eliminate common sources of clinical trial delay and failure.

The development of mRNA vaccines during the COVID-19 pandemic has opened the door for the application of mRNA technology in many other fields.

Oncology

Due to their genetic instability, cancers often display neoantigens, which distinguish them from healthy tissue. This means the immune system can be trained to destroy cancer cells, similarly to how it destroys an invading pathogen. mRNA cancer vaccines work by delivering mRNA that encodes specific cancer antigens, which in turn trains the immune system to recognize and attack cancer cells. mRNA vaccines represent a leading technology for personalized medicine approaches to cancer treatment and there are over one hundred clinical trials underway to evaluate mRNA therapies for the treatment of diverse cancer types.

Infectious Disease

mRNA technologies have the potential for rapid design and development, which makes them incredibly useful as a therapy against infectious diseases. mRNA can theoretically code for a virtually limitless number of unique proteins. This means it can be readily applied to address emerging pathogens, such as during the COVID-19 pandemic, but also allows them to be employed for rapidly evolving diseases like HIV and influenza viruses. mRNA vaccines could speed up the annual development of flu vaccines, freeing up resources and ensuring efficient vaccine rollouts. An mRNA-based vaccine against the Epstein-Barr virus is in phase I trials.

Autoimmune Diseases

These diseases occur when the immune system attacks healthy host tissue. mRNA technologies could be implemented to induce immune tolerance and prevent inflammatory reactions against self-antigens or specific tissue types. By encoding proteins or peptides that modulate immune responses, mRNA therapies can promote the generation of regulatory immune cells or tolerogenic proteins. An mRNA-based therapy from Moderna that encodes interleukin 2 to expand T-regulatory cell populations is now in clinical development.

doctor looking at a vertebra radiography

Genetic Disorders

Until now, mRNA technology has primarily focused on its use in vaccines and augmenting the immune system to protect against infectious diseases. However, mRNA technology is incredibly versatile and can be used for other applications. Many diseases arise from the production of malfunctioning proteins caused by underlying genetic mutations. mRNA therapies allow for the delivery of healthy copies of mRNA to patients, which are then translated into functional proteins. This could be particularly important for diseases like cystic fibrosis (CF), which arise from mutations in a single gene and whose mutational landscape is well-defined. This would enable transient treatment of the condition but would likely not provide a lasting benefit compared to integrating gene therapies. An early-stage clinical trial is underway to assess the effect of mRNA encoding healthy copies of the causal protein in CF on improving lung function.

Moreover, mRNA technology can be utilized to deliver gene-editing tools like the CRISPR-Cas9 system to treat various genetic disorders. This approach can be used either by delivering the therapy directly to patients or by modifying their cells outside the body and then reintroducing them.

Regenerative Medicine

mRNA therapies could be used in regenerative medicine to encode proteins that aid in tissue repair or direct the body's repair mechanisms to specific areas. This approach could be revolutionary in cardiology, as damaged heart tissue does not heal as effectively as other tissues in the body. This approach may offer advantages over gene therapies, as it allows for dosage adjustments based on individual patient needs and can be discontinued once the damaged tissue is healed.

Diabetes

mRNA could be used to treat diabetes in several ways. One option is to use mRNA to provide beta cells with instructions for regeneration and to increase the proliferation and differentiation of beta cell precursors. Promising results have been observed in mice where injection with mRNA promoted diabetic wound healing. mRNA could also be used for gene editing to help resolve diabetes cases with a genetic origin.

Challenges to Overcome

Despite advances in mRNA technology and improvements in the efficiency of its production, the technology is far from optimized, with many essential areas still needing to be addressed.

Slow Production

Current processes have not fully implemented automation and continuous processing, which leads to slower mRNA therapeutic development. Production inefficiencies can also increase the number of freeze-thaw cycles the mRNA is exposed to during development, reducing production yield and impacting quality.

Storage

Larger-scale mRNA production faces issues with long-term storage. Lyophilization has emerged as a way to store encapsulated mRNA therapies at higher temperatures, which may help alleviate logistical problems in the distribution chain. However, this storage method is known to affect encapsulation efficiency.

Costs

Automation will help to reduce the costs of large-scale production; however, smaller-scale production of patient-specific mRNA will likely continue to be very expensive and prone to the inefficiencies of lower-scale output. This could limit the use of mRNA for personalized medicine, while applications like large vaccination programs will be less affected.

Immunogenicity and Toxicity

Scaling quality control processes such as chromatography is another challenge that must be overcome to remove inappropriate immunostimulatory molecules from mRNA therapeutic formulations. Some mRNA delivery systems tend to accumulate in the liver and lead to hepatic toxicity. Thus, developing technologies that target LNPs to specific organs is important.

METTLER TOLEDO provides advanced weighing and analytical instrumentation that help ensure accuracy during mRNA therapy development workflows. Furthermore, our automated solutions reduce variability and facilitate efficient process scaling that lowers costs and the chances of human error. Collectively, these platforms mean METTER TOLEDO offers streamlined, resource-efficient mRNA production, which is facilitated through partnerships with global bioprocess leaders Agilent and robotics leaders ABB.

Modern laboratory instrumentation plays a crucial role in ensuring regulatory compliance by providing the precision necessary for developing advanced therapies. Furthermore, cutting-edge analytical platforms support data traceability, consistency, and quality assurance, which are vital for maintaining regulatory standards throughout the development process.

As mRNA technologies advance and become more practical therapeutic applications, the need for regulatory standardization is growing increasingly urgent. Variations in the manufacturing process can result in unacceptable levels of immunostimulatory contaminants, such as the DNA template used for mRNA production. Furthermore, uncertainty in regulatory requirements makes it challenging for companies to manage clinical and preclinical testing efficiently. For instance, while there have been innovations in microfluidic systems for encapsulating mRNA, no standardized process exists, and the procedures are customized to specific devices. Implementing standardized analytical techniques for testing and producing mRNA technologies will help ensure these therapies' safety, effectiveness, and consistency across different manufacturers. Clarification on gold-standard protection methods will simplify decision-making and allow a more focused effort toward alleviating production bottlenecks and exploring new therapeutic avenues.

scientist looking at a computer and smiling

mRNA technology has already revolutionized vaccine development, and its potential extends far beyond infectious diseases. With advancements in mRNA stability, delivery systems, and production efficiency, mRNA therapies are poised to transform oncology, autoimmune disorders, rare genetic diseases, and chronic conditions like diabetes and cardiovascular disease. Despite these exciting possibilities, key challenges, such as immunogenicity, large-scale production inefficiency, and quality control, must be addressed to fully unlock mRNA’s therapeutic potential. As research continues and regulatory standards evolve, mRNA technology stands on the cusp of becoming a versatile, powerful tool in modern medicine, offering hope for personalized treatments and more efficient healthcare solutions.