The global mRNA market is expanding rapidly beyond SARS-CoV-2 because over 599 million people received primary doses of Moderna’s Spikevax and Pfizer/BioNTech’s Comirnaty, establishing regulatory acceptance and driving 316 active RNA drug candidates into development across 190 companies.
Next-generation self-amplifying mRNA (saRNA) and circular RNA (circRNA) reduce dosage thresholds because saRNA enables intracellular replication for equivalent efficacy at lower doses, while circRNA provides enhanced structural stability and extended protein expression compared to conventional linear mRNA.
Late-stage mRNA infectious disease pipelines target historically difficult pathogens because Moderna’s mRNA-1345 achieved 83.7% efficacy in Phase III RSV trials, while novel candidates target complex antigens for cytomegalovirus (CMV), universal influenza, and combination SARS-CoV-2/flu formulations.
The biopharmaceutical sector drives the majority of RNA clinical research because industrial sponsors control over 61% of infectious disease trial registrations, leveraging protein replacement, gene editing delivery (CRISPR), and personalized cancer neoantigen platforms.
1 COVID-19 Vaccines Propelled mRNA into the Spotlight
1.1 Development of mRNA technology for use in therapeutic and vaccine applications has been underway for decades. That investment, coupled with extensive government funding and support and cooperation among all members of the biopharma industry value chain, made it possible to bring the two successful mRNA vaccines against the SARS-nCoV-2 virus to the market in record time during the COVID-19 pandemic. By February 2024, an estimated 13.5 billion vaccine doses had been administered globally, representing vaccination of 70.6% of the world’s population.[1] As of May 2023, the Centers for Disease Control and Prevention (CDC) reported that over 599 million people had been dosed with the two leading mRNA vaccines, Spikevax (Moderna) and Comirnaty (Pfizer/BioNTech).[2] Although the pandemic has receded, the lasting impact of COVID-19 on mRNA technology will likely be its rapidly expanded acceptance by regulators and payers alike.
1.2 Further drivers of the interest in mRNA technology include its modularity[3] and ability to express multiple, different proteins and/or protein subunits, allowing simultaneous targeting of several variants of the same pathogen and/or several different pathogens.[4]
1.3 Beyond development efforts on the drugs or vaccines themselves, research efforts are also focused on numerous adjacent areas, including optimizing stability and delivery, as well as leveraging more advanced forms such as self-amplifying mRNA (saRNA), which enables lower doses to achieve the same efficacy or higher doses to address indications not possible with traditional mRNA.[5] Adjacent to the cancer vaccine space, there is also work being done with respect to identifying the right neoantigens, finding ways to overcome the suppressive activities of the tumor microenvironment in solid tumors, and enhancing delivery of mRNA into the right antigen-presenting cells.[5]
2 Market Landscape and Definitions
2.1 The mRNA market comprises two primary product categories: therapeutics and vaccines. mRNA vaccines work by delivering a genetic blueprint that instructs cells to produce an antigen, typically a viral protein, which then triggers an immune response. This approach has been widely validated by the COVID-19 pandemic, where mRNA vaccines from Moderna and Pfizer/BioNTech demonstrated both rapid development timelines and high efficacy. Products in development are now targeting a broad array of virus-borne diseases (influenza, Zika, dengue, rabies, HIV, hepatitis, and Venezuelan equine encephalitis, among others), as well as bacterial infections, such as Staphylococcus and tuberculosis.
2.2 In contrast, mRNA therapeutics involve delivering genetic instructions that encode for functional proteins intended to replace or supplement those missing or malfunctioning in a patient’s body. Therapeutic vaccines against many types of cancer often include personalized treatments based on the tumor characteristics of individual patients. Therapies are being actively explored across oncology, rare diseases, and metabolic and autoimmune conditions, among other indications.[6] Development is underway for drug products functioning via protein or gene replacement or as delivery agents for gene-editing tools, including CRISPR components and human retrovirus-like proteins that can implement controlled edits.[3][5][7][8] Products in development that are indicated for rare and genetic conditions are often touted as potential curative treatments, and not just therapeutics.
2.3 The mRNA market can be segmented by application, technology type, and end user. Application-wise, it is broadly divided into vaccines and therapeutics, each with distinct development pipelines and market dynamics. From a technology perspective, conventional mRNA remains dominant, but next-generation formats are gaining traction. saRNA offers lower dosage requirements by enabling replication within cells, while circRNA provides improved stability and extended protein expression.[9] These advancements are expanding the functional range of mRNA beyond traditional applications.
2.4 End users of mRNA-based products and services span pharmaceutical and biotechnology companies, academic and research institutions, and governmental organizations. While large pharma has played a leading role in pandemic-era vaccine development and now increasingly in oncology and personalized immunotherapy, smaller biotechs are often the source of innovation in RNA modalities and platform technologies. Academic centers and government programs remain essential for foundational research, early-stage development, and pandemic preparedness initiatives. Together, these stakeholders shape a complex but rapidly converging market ecosystem.
3 Coronavirus Isn’t the Only Virus
3.1 Since the emergency use authorization (EUA) of mRNA-based COVID-19 vaccines, many other mRNA-based candidates have rapidly progressed through the clinic. As of July 28, 2023, 316 RNA treatments were actively being investigated by 190 companies, according to Clarivate’s Cortellis Competitive Intelligence Database, with 57% at the discovery and preclinical stage, 39% undergoing clinical study, 1.9% at the pre-registration stage, and 1.6% having received approvals.[10] Of the 125 candidates in the clinic, approximately two-thirds were vaccines and one‑third therapeutics. Most of the later-stage candidates and products are COVID-19 vaccines.[10]
3.2 Some viruses have proven difficult to develop vaccines against through traditional methods. An immune challenge with the respiratory syncytial virus (RSV) antigen often creates a dangerous immune response in newborns.[11] With the advent of mRNA technology, researchers now have the potential to express the proper RSV antigen, which will generate a safer response in newborns or when administered to their nursing mothers. A universal flu vaccine has not been possible to date because the conserved influenza antigen is not stable enough to deliver so that it will elicit an immune response. We have instead relied on antigens that change sequence every year to create seasonal flu vaccines. Expression of the core, conservative antigen from the proper immune cells enables the possibility of developing a flu vaccine that could be effective over multiple years.[12]
3.3 Moderna, an early leader in the development of mRNA vaccines for COVID-19, has built a portfolio of additional vaccine candidates. Their candidate mRNA-1345 against RSV in older adults has completed a phase III trial that demonstrated vaccine efficacy of 83.7%. The company filed for regulatory approval based on the data in July 2023.[13]
3.4 Moderna’s mRNA influenza vaccine candidate mRNA-1010 is also in late-stage trials. The company announced in September 2023 that the vaccine met its primary endpoint in a phase III trial, while separate phase I/II data indicated higher performance than Fluzone HD.[14] Two more phase III trials, one for mRNA-1647, a first-in-class vaccine against cytomegalovirus (CMV), and one for mRNA-1283, a next-generation COVID-19 vaccine, were also launched in 2023.
3.5 In addition to the COVID-19 vaccines, Pfizer and BioNTech are developing an mRNA-based combination vaccine against influenza and COVID-19. The companies announced in October 2023 that lead formulations evaluated in a phase I/II study demonstrated robust immune responses to influenza A, influenza B, and SARS-CoV-2 strains. A pivotal phase III trial is planned in the near future.[15]
3.6 Moderna, Pfizer, and BioNTech are not the only innovators working to develop additional vaccines. Nice Insight performed a detailed analysis of RNA-based clinical trials, for both infectious diseases and noninfectious disease. The data is presented in a separate Nice Insight (link to RNA trials) article. As of February 15, 2024, 92 different entities are sponsoring at least one trial for an infectious disease using an RNA modality. We learned in this analysis that over 61% of the sponsors of infectious disease trials are industrial.
FAQs
What is the primary difference between mRNA vaccines and mRNA therapeutics?
mRNA vaccines deliver genetic blueprints instructing cells to synthesize viral antigens that trigger protective immune responses against infectious pathogens. Conversely, mRNA therapeutics deliver genetic instructions encoding functional proteins to replace or supplement missing or defective native proteins, targeting oncology, rare genetic disorders, and autoimmune conditions through mechanisms like protein replacement and CRISPR gene editing.
How do self-amplifying mRNA and circular RNA improve upon conventional linear mRNA?
Self-amplifying mRNA (saRNA) enables cellular replication of the genetic sequence, allowing significantly lower therapeutic doses to achieve equivalent or superior efficacy. Circular RNA (circRNA) features a closed-loop structure that resists enzymatic degradation, providing enhanced molecular stability and prolonged protein expression duration compared to traditional linear biopolymers.
Why is mRNA technology uniquely suited for developing universal influenza and RSV vaccines?
mRNA platforms express stabilized, highly conserved core viral antigens that traditional subunit or inactivated production methods struggle to deliver effectively. This capability allows vaccines to target invariant regions of the virus—such as the conservative core antigens in influenza or specific respiratory syncytial virus (RSV) proteins—preventing dangerous immune reactions while generating multi-year broad neutralization.
What role do small biotechs play compared to large pharma in the mRNA market ecosystem?
Small biotechnology companies act as the primary engines of innovation for novel RNA modalities, platform technologies, and specialized delivery vectors. Large biopharmaceutical corporations typically drive late-stage clinical trials, regulatory filings, global commercialization, and mass production, while academic and government institutions support foundational discovery and pandemic preparedness research.
How are personalized mRNA cancer vaccines engineered to target solid tumors?
Personalized mRNA cancer vaccines encode patient-specific neoantigens identified through sequencing the unique mutational profile of an individual's tumor. Once injected, the mRNA instructs antigen-presenting cells to display these unique peptides, training T-cells to identify, attack, and overcome the suppressive tumor microenvironment characteristic of solid malignancies.
What is the clinical status of combination mRNA vaccines for respiratory pathogens?
Combination mRNA vaccines are undergoing advanced Phase II and Phase III clinical trials to provide simultaneous immunization against multiple respiratory viruses. Leading formulations from companies like Pfizer, BioNTech, and Moderna combine genetic sequences targeting seasonal influenza strains (A and B) alongside SARS-CoV-2, demonstrating robust dual immune responses in early trial cohorts.
