Nigel Theobald, Chief Executive Officer, N4 Pharma
The success of mRNA-based COVID-19 vaccines has accelerated RNA therapeutic innovation into a diverse range of applications, including gene editing and personalized cancer treatments. However, the instability and poor cellular uptake of RNA molecules remains a key challenge, necessitating advanced delivery systems for safe and effective targeting.
One promising area is oral RNA therapeutics for inflammatory bowel disease (IBD). While small interfering RNA (siRNA) drugs can selectively silence disease-causing genes, they degrade rapidly in the gastrointestinal (GI) tract, making oral delivery challenging. Nanoparticle delivery systems are being engineered to overcome this and protect oligonucleotides, such as siRNA, from enzymatic degradation to facilitate targeted delivery and enhance its absorption via the gut.
In vivo proof-of-concept studies using silica-based nanoparticle Nuvec® (non-lipid and non-viral) have shown preclinical potential for delivering siRNA molecules to target cells and confirmed successful oral administration of Nuvec loaded with DNA plasmid for ovalbumin. Together, these demonstrate the potential for oral delivery of oligonucleotides using nanoparticle delivery systems. Directly delivering RNA therapy to the affected site could revolutionize IBD treatment by reducing side effects and boosting efficacy. As research advances, delivery systems therefore will be instrumental to expanding the scope of RNA-based medicine.
Erica Cirri, Ph.D., Projects Leader, Tebubio
The rapid development of mRNA vaccines for SARS-CoV-2 transformed the biomedical landscape, showcasing their potential for adaptable, precise, and scalable therapeutic solutions.
Most mRNA vaccines currently in clinical trials are against high-impact viral, bacterial, and protozoal pathogens. But the future of mRNA therapeutics lies beyond infectious diseases, with the technology being explored for applications in oncology and genetic disorders, as well as personalized medicine and rare diseases.
Several mRNA cancer vaccines have demonstrated promising results, particularly in high-risk melanoma. mRNA-4157 (V940, Moderna) is an example of personalized cancer vaccine, encoding up to 34 neoantigens selected based on sequencing data from patients' tumors.
Replacement therapies, where mRNAs are administered to compensate for a defective gene or to supply therapeutic proteins, have reached the clinical stage for cystic fibrosis, propionic acidemia, and ornithine transcarbamylase deficiency.
Genome and RNA editing are growing fields with significant innovation, including the delivery of synthetic mRNA to encode nucleases and base editors. The initial clinical trials for RNA editing have primarily targeted rare diseases, but the transient nature of this approach opens the door to broader therapeutic applications.
In coming years, advancements in targeting precision and RNA manufacturing will further expand the reach of these groundbreaking therapies.
Benjamin Hein, Head of Life Science Services, MilliporeSigma, the Life Science business of Merck KGaA, Darmstadt, Germany
On the therapeutic front, mRNA is driving advancements in oncology, rare diseases, and protein replacement therapies. One of the most exciting areas is personalized cancer immunotherapy and in vivo CAR-T, where mRNA-based treatments can program the immune system to recognize and attack tumor-specific antigens.
Additionally, mRNA is being investigated for protein replacement therapies in rare genetic disorders, providing a means to temporarily produce missing or defective proteins. It is also emerging as a significant tool in gene editing for genetic diseases.
Sebastián Arana, Head of Process Solutions, MilliporeSigma, the Life Science business of Merck KGaA, Darmstadt, Germany
The rapid evolution of mRNA technology is unlocking new possibilities far beyond COVID vaccines, paving the way for groundbreaking applications in both vaccine development and therapeutics. Beyond vaccines and therapeutics, mRNA is making strides in regenerative medicine and autoimmune disease treatment. Researchers are exploring its potential to reprogram cells for tissue repair and regeneration, holding promise for conditions, such as myocardial infarction and neurodegenerative diseases. Innovations in delivery systems — such as lipid nanoparticles and polymer-based carriers — are enhancing the stability, targeting, and efficacy of mRNA-based therapies. As the field advances, the expanding portfolio of mRNA applications is poised to reshape treatment paradigms, making precision medicine more accessible and adaptable to unmet medical needs.
Dr. Carsten Rudolph, Co-Founder and Chief Executive Officer, Ethris
mRNA technology is rapidly evolving beyond its success in vaccines, unlocking transformative therapeutic applications across medicine. A key advancement is in aerosolized mRNA therapies, which use lipid nanoparticles (LNPs) engineered for enhanced delivery to the respiratory tract, enabling direct treatment of respiratory conditions while minimizing systemic exposure or off-target effects. This approach has the potential to revolutionize respiratory disease management, with candidates targeting viral exacerbations in asthma and chronic obstructive pulmonary disease (COPD) by encoding antiviral proteins. mRNA treatment is also expanding into rare genetic disorders, such as primary ciliary dyskinesia or cystic fibrosis, where therapies replace missing or defective proteins to restore function. Beyond pulmonary therapies, antiviral mRNA candidates are being explored for the treatment of intravaginal, ocular, and systemic infections, including those responsible for viral haemorrhagic fevers (VHFs). In oncology, mRNA platforms are being paired with checkpoint inhibitors to train immune systems against tumors. Other applications in development include regenerative medicines restoring dysfunctional enzymes in inherited metabolic diseases or curing critical bone fractures. Beyond specific therapeutic areas, efforts focus on improving mRNA stability to decrease reliance on cold-chain logistics and enable broader distribution.
mRNA therapies are on the cusp of transforming millions of lives, paving the way for a new era in medical innovation.
Sönke Stocker, Executive Director of Innovation and Strategic Growth for mRNA, Lonza
New opportunities for mRNA technology are emerging rapidly, expanding into applications well beyond vaccines. This is demonstrated by the over 300 active studies of mRNA therapeutics to treat various diseases. One of the most exciting areas is gene editing, where mRNA is advancing cell and gene therapies. This includes in vivo gene editing for metabolic and genetic diseases and CAR-T therapies.
In vivo mRNA therapies are increasingly being explored as a potential alternative to viral vector delivery — not only because of various safety profile considerations for viral vectors and the lack of DNA integration into the genome when using mRNA for gene editing, but also because of better manufacturing scalability for mRNA and thus the potential for lower production costs. Beyond gene editing, mRNA is being explored for protein replacement therapies, particularly for metabolic diseases, enabling patients to produce essential proteins transiently. While most of these products are in pre-clinical or early clinical stages, the potential is significant and can help provide meaningful treatment solutions to patients living with debilitating diseases.
At Lonza, we are deeply engaged in mRNA formulation and encapsulation technologies to support these expanding applications. For example, our work in LNP manufacturing ensures that mRNA therapeutics reach their targets efficiently while maintaining stability. We are also exploring advanced delivery solutions like spray drying for pulmonary and intranasal delivery of mRNA payloads and targeted LNPs — further broadening the scope of mRNA-based drug delivery. As these innovations advance, we focus on optimizing scalability, stability, and delivery efficiency to help bring the next generation of mRNA therapies to patients worldwide.
Sungyul Lee, Ph.D., Principal Scientist and Senior Director of GT Technology Lab, Samsung Biologics
As mRNA technology continues to advance, managing manufacturing complexity and scalability remain critical challenges. To overcome these hurdles, cumulative experiences and knowledge of the technology’s key components will help researchers implement good practices and obtain reliable data. Additionally, innovations such as cell-free DNA synthesis and high-throughput LNP formulations enable scientists to accelerate production timelines and increase success rates. To address the clinical shortcomings of mRNA technology, continuous improvement is necessary. This can entail the utilization of self-amplifying RNA (saRNA) and circular RNA (circRNA), as well as experimenting with different types of capping and polyA tails configurations. By addressing the technology's shortcomings, the versatility of mRNA can be fully realized, enhancing the efficacy of mRNA vaccines and therapeutics.
Looking towards the future, therapeutic cancer vaccines, genetic disorders, and neurological diseases are expected to become prominent areas of focus for mRNA drugs. As this shift occurs, disease portfolios must evolve alongside continuous technological innovation in mRNA half-life, non-viral delivery functionality, reactogenicity, and organ-specificity of LNPs. Overall, the successful adoption of mRNA technology will rely heavily on addressing these challenges and investing in innovations to maximize its versatility.
Samuel Deutsch, Ph.D., Chief Scientific Officer, Nutcracker Therapeutics
mRNA technology is rapidly expanding beyond its initial focus on infectious diseases, offering potential new solutions for many afflictions, including cancer, autoimmune diseases, genetic diseases, and more. More specifically, personalized cancer therapeutics (PCTs) are one area in which mRNA shows great promise in revolutionizing treatment. mRNA can be used to instruct cells to produce antigens specific to the patient’s own tumor, helping the immune system identify and attack the cancer more effectively. This approach has shown promise in clinical trials, as evidenced by exciting data from Merck and Moderna’s mRNA therapeutic for melanoma, and BioNTech and Roche’s mRNA therapeutic for pancreatic cancer, in addition to others. As the technology advances, mRNA-based PCTs could serve as a powerful complement to other cancer treatments, such as checkpoint inhibitors, providing the multi-pronged approach needed to effectively fight cancer.