Circular RNA Therapeutics in 2025: Transforming RNA Medicine with Breakthroughs in Stability, Delivery, and Disease Targeting. Explore the Market Forces and Innovations Shaping the Next Five Years.

• Executive Summary: Circular RNA Therapeutics Landscape 2025
• Market Size, Growth Rate, and Forecasts (2025–2030)
• Key Players and Strategic Partnerships
• Technological Innovations: Synthesis, Delivery, and Targeting
• Pipeline Analysis: Leading Candidates and Clinical Milestones
• Regulatory Environment and Approval Pathways
• Intellectual Property and Patent Trends
• Investment, Funding, and M&A Activity
• Challenges: Manufacturing, Scalability, and Safety
• Future Outlook: Opportunities and Market Drivers Through 2030
• Sources & References

Executive Summary: Circular RNA Therapeutics Landscape 2025

Circular RNA (circRNA) therapeutics have rapidly emerged as a transformative modality in the RNA-based drug development landscape, with 2025 marking a pivotal year for both preclinical innovation and the first clinical milestones. CircRNAs, characterized by their covalently closed loop structures, offer enhanced stability and translational efficiency compared to linear mRNA, positioning them as promising candidates for next-generation therapeutics in areas such as oncology, rare diseases, and vaccines.

In 2025, the sector is defined by a surge in investment, strategic partnerships, and the initiation of first-in-human studies. Orna Therapeutics, a pioneer in the field, has advanced its lead circular RNA program into early clinical development, targeting solid tumors with its proprietary oRNA™ technology. The company’s platform leverages the unique properties of circRNA to enable potent and durable protein expression, with preclinical data demonstrating superior efficacy and safety profiles relative to traditional mRNA approaches. Orna’s collaboration with Merck & Co., Inc. (MSD) underscores the pharmaceutical industry’s confidence in circRNA, with a partnership valued at up to $3.5 billion to co-develop novel circRNA-based vaccines and therapeutics.

Other notable players include Lantern Pharma, which is exploring circRNA constructs for targeted cancer therapies, and Aaron Pharma, focusing on rare genetic disorders. Meanwhile, Moderna, Inc. and BioNTech SE have both disclosed internal circRNA research programs, aiming to expand their RNA technology portfolios beyond mRNA, with early-stage data anticipated in the next 12–24 months.

The regulatory landscape is also evolving, with agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) engaging with developers to establish guidelines for circRNA-based products. Key challenges remain, including scalable manufacturing, delivery optimization, and immunogenicity assessment, but advances in synthetic biology and nanoparticle delivery systems are rapidly addressing these hurdles.

Looking ahead, the next few years are expected to see multiple circRNA candidates entering clinical trials, with initial readouts likely by 2026–2027. The field’s trajectory suggests that circRNA therapeutics could soon complement or even surpass mRNA-based modalities in certain indications, driven by their unique biological advantages and growing industry momentum.

Market Size, Growth Rate, and Forecasts (2025–2030)

The circular RNA (circRNA) therapeutics market is emerging as a significant frontier in RNA-based medicine, with 2025 marking a pivotal year for both research and early commercial development. CircRNAs, characterized by their covalently closed loop structures, offer enhanced stability and unique regulatory functions compared to linear RNAs, making them attractive candidates for next-generation therapeutics. As of 2025, the market remains in its nascent stage, with most activity centered on preclinical and early clinical development. However, the sector is poised for rapid expansion, driven by increasing investment, technological advancements, and the success of related RNA modalities.

Key players in the circRNA therapeutics space include Orna Therapeutics, a biotechnology company pioneering the development of circular RNA-based medicines. Orna has advanced its proprietary oRNA™ technology platform, which enables the design and delivery of circular RNA constructs for protein replacement, gene editing, and immuno-oncology applications. In 2023, Orna announced a strategic collaboration with Merck & Co., Inc. (known as MSD outside the United States and Canada), valued at up to $3.5 billion, to develop and commercialize novel circular RNA therapies for oncology and infectious diseases. This partnership underscores the growing confidence of major pharmaceutical companies in the therapeutic potential of circRNAs.

Another notable entrant is Lantern Pharma Inc., which is exploring circRNA-based approaches within its AI-driven drug discovery platform. Additionally, Aaron Pharma and several academic spinouts are actively developing circRNA therapeutics, particularly for rare genetic disorders and cancer.

Market projections for circRNA therapeutics from 2025 to 2030 anticipate a compound annual growth rate (CAGR) exceeding 30%, reflecting both the low base and the high expectations for clinical translation. By 2030, the global circRNA therapeutics market is expected to reach several billion USD in value, contingent on successful clinical outcomes and regulatory approvals. The market’s growth will be fueled by expanding pipelines, increased funding from both venture capital and strategic partnerships, and the maturation of manufacturing and delivery technologies.

Looking ahead, the next few years will be critical for the validation of circRNA therapeutics in human trials. The first wave of clinical data, expected between 2025 and 2027, will shape investor sentiment and influence the pace of market expansion. If early results demonstrate safety and efficacy, circRNA therapeutics could rapidly transition from experimental to mainstream, mirroring the trajectory seen with mRNA vaccines and therapies. The sector’s outlook remains highly optimistic, with leading companies and stakeholders committed to advancing this innovative modality toward commercialization.

Key Players and Strategic Partnerships

The field of circular RNA (circRNA) therapeutics is rapidly evolving, with 2025 marking a pivotal year for both established biotechnology firms and emerging startups. The sector is characterized by a surge in strategic partnerships, licensing agreements, and investments aimed at accelerating the development and commercialization of circRNA-based medicines. These collaborations are essential for overcoming technical challenges such as efficient delivery, scalable manufacturing, and regulatory approval.

Among the most prominent players, Orna Therapeutics stands out as a pioneer, having developed proprietary circular RNA technology platforms. In 2022, Orna entered a landmark collaboration with Merck & Co., Inc. (MSD outside the US and Canada), valued at up to $3.5 billion, to develop and commercialize novel circRNA vaccines and therapeutics for infectious diseases and oncology. This partnership is expected to yield its first clinical candidates in 2025, with both companies investing heavily in expanding manufacturing capabilities and preclinical pipelines.

Another key player, Lantern Pharma, is leveraging artificial intelligence to identify and optimize circRNA targets for cancer therapy. Lantern’s strategic collaborations with academic institutions and contract research organizations are anticipated to accelerate the translation of circRNA discoveries into clinical-stage assets over the next few years.

In Europe, RiboCure Pharmaceuticals is advancing a portfolio of circRNA-based therapeutics targeting rare genetic disorders. The company has established partnerships with leading research hospitals and is actively seeking alliances with larger pharmaceutical firms to support late-stage development and commercialization.

Meanwhile, AbbVie has signaled its interest in the circRNA space through investments in early-stage biotech companies and exploratory research collaborations. These efforts are part of a broader strategy to diversify its RNA therapeutics pipeline beyond traditional mRNA and siRNA modalities.

Looking ahead, the next few years are expected to witness further consolidation and cross-sector partnerships, as companies seek to pool expertise in RNA biology, delivery technologies, and regulatory affairs. The entry of major pharmaceutical companies, combined with the agility of specialized biotech firms, is likely to accelerate the clinical translation of circRNA therapeutics. As clinical data emerges and regulatory pathways become clearer, strategic alliances will remain a cornerstone of progress in this dynamic sector.

Technological Innovations: Synthesis, Delivery, and Targeting

The field of circular RNA (circRNA) therapeutics is experiencing rapid technological innovation, particularly in the areas of synthesis, delivery, and targeting. As of 2025, several biotechnology companies and research organizations are advancing the development of scalable and efficient methods for circRNA production, as well as novel delivery platforms tailored to the unique properties of these molecules.

One of the primary challenges in circRNA therapeutics has been the efficient and precise synthesis of circularized RNA molecules. Recent advances have focused on enzymatic ligation and rolling circle transcription methods, which enable the production of high-purity circRNAs with minimized linear RNA contaminants. Companies such as Orna Therapeutics have developed proprietary circular RNA synthesis platforms that leverage these techniques, aiming to improve the stability and translational efficiency of therapeutic circRNAs. Orna’s oRNA™ technology, for example, is designed to generate highly stable and translatable circRNAs for use in protein replacement therapies and vaccines.

Delivery remains a critical hurdle for RNA-based therapeutics, and circRNAs present unique opportunities and challenges due to their covalently closed structure, which confers increased resistance to exonucleases. Lipid nanoparticle (LNP) technology, which has been successfully employed in mRNA vaccines, is being adapted for circRNA delivery. Moderna, Inc. and BioNTech SE are both actively exploring LNP formulations optimized for circRNA payloads, with preclinical data suggesting improved pharmacokinetics and reduced immunogenicity compared to linear mRNA. These companies are leveraging their established expertise in nucleic acid delivery to accelerate the translation of circRNA therapeutics into clinical trials.

Targeting specificity is another area of innovation, with researchers developing modular circRNA constructs that incorporate tissue-specific aptamers or ligand-binding domains. This approach aims to direct circRNA therapeutics to particular cell types or disease sites, thereby enhancing efficacy and minimizing off-target effects. Orna Therapeutics and Aarna Therapeutics are among the companies investigating targeted circRNA delivery for oncology and rare genetic disorders, utilizing both proprietary sequence elements and advanced delivery vehicles.

Looking ahead, the next few years are expected to see the first circRNA-based therapeutics enter early-phase clinical trials, with a focus on indications such as cancer immunotherapy, protein replacement, and infectious disease vaccines. The convergence of improved synthesis methods, advanced delivery systems, and precision targeting strategies is poised to accelerate the clinical translation of circRNA therapeutics, potentially establishing a new class of RNA medicines with broad applicability and enhanced durability.

Pipeline Analysis: Leading Candidates and Clinical Milestones

The field of circular RNA (circRNA) therapeutics is rapidly advancing, with several companies progressing from preclinical research to early clinical development as of 2025. CircRNAs, characterized by their covalently closed loop structures, offer unique advantages such as enhanced stability and reduced immunogenicity compared to linear RNAs, making them attractive candidates for next-generation RNA therapeutics.

Among the frontrunners, Orna Therapeutics has emerged as a leader, leveraging its proprietary oRNA™ technology to develop circular RNA-based medicines. In 2023, Orna announced a strategic collaboration with Merck & Co., Inc. (MSD outside the US and Canada) to develop and commercialize novel circRNA therapies for infectious diseases and oncology, with a deal valued at up to $3.5 billion in milestones and upfront payments. Orna’s lead candidate, ORN-101, is designed for in vivo delivery of chimeric antigen receptor (CAR) constructs to treat hematological malignancies. As of early 2025, ORN-101 is advancing through IND-enabling studies, with first-in-human trials anticipated within the next 12–18 months.

Another notable player, Lantern Pharma, is exploring circRNA platforms for targeted cancer therapies, focusing on leveraging the unique translational capabilities of circRNAs to produce therapeutic proteins in situ. While Lantern’s circRNA programs remain in the preclinical stage, the company has signaled plans to initiate IND submissions by late 2025, targeting solid tumors with high unmet medical need.

In Europe, Thermo Fisher Scientific and Evotec SE are supporting the sector through manufacturing partnerships and technology platforms, enabling scalable production and optimization of circRNA constructs for both research and clinical applications. These collaborations are expected to accelerate the transition of circRNA candidates from bench to bedside, addressing key challenges in delivery and manufacturing.

Looking ahead, the next few years are poised to witness the first clinical data readouts from circRNA-based therapeutics, particularly in oncology and rare genetic diseases. The sector is also seeing increased interest from major pharmaceutical companies, as evidenced by recent partnership and licensing deals. Regulatory agencies are beginning to engage with developers to establish guidelines for circRNA therapeutics, which will be critical for the advancement of clinical programs.

• 2025–2026: Anticipated initiation of first-in-human trials for lead circRNA candidates (e.g., ORN-101).
• 2026–2027: Early clinical data expected, informing safety, tolerability, and preliminary efficacy.
• Ongoing: Expansion of manufacturing capabilities and regulatory framework development.

Overall, the pipeline for circular RNA therapeutics is entering a pivotal phase, with leading candidates approaching clinical milestones that could validate the promise of this novel modality in the coming years.

Regulatory Environment and Approval Pathways

The regulatory environment for circular RNA (circRNA) therapeutics is rapidly evolving as these novel modalities transition from preclinical research to clinical development. As of 2025, no circRNA-based therapeutic has yet received full regulatory approval, but several candidates are advancing through early-stage clinical trials, prompting regulatory agencies to clarify and adapt their frameworks for this emerging class of RNA medicines.

In the United States, the U.S. Food and Drug Administration (FDA) is actively engaging with developers of circRNA therapeutics to define requirements for Investigational New Drug (IND) applications. The FDA’s Center for Biologics Evaluation and Research (CBER) is leveraging its experience with mRNA and other nucleic acid-based therapies to guide the evaluation of circRNA products, focusing on aspects such as manufacturing consistency, delivery systems, immunogenicity, and long-term safety. The agency has signaled openness to adaptive regulatory pathways, including Fast Track and Breakthrough Therapy designations, for circRNA candidates addressing serious or unmet medical needs.

In the European Union, the European Medicines Agency (EMA) is similarly developing guidance for circRNA therapeutics, building on its established procedures for advanced therapy medicinal products (ATMPs) and RNA-based drugs. The EMA’s Committee for Advanced Therapies (CAT) is expected to play a central role in scientific advice and protocol assistance for circRNA developers, particularly regarding quality, safety, and efficacy standards. The EMA is also encouraging early dialogue with sponsors to address the unique challenges of circRNA, such as novel delivery vectors and potential off-target effects.

Several biotechnology companies are at the forefront of circRNA therapeutic development and are actively engaging with regulators. Orna Therapeutics, a leader in the field, has announced plans to initiate first-in-human trials for its lead circRNA candidate targeting oncology indications in 2025. Laronde, another prominent player, is advancing a pipeline of eRNA (endless RNA, a proprietary circRNA platform) therapeutics for rare diseases and chronic conditions, with preclinical data being shared with regulatory authorities to inform future clinical trial designs. aoaDx Inc. is also developing circRNA-based diagnostics and therapeutics, particularly in oncology, and is working closely with both the FDA and EMA to ensure compliance with evolving regulatory expectations.

Looking ahead, the next few years are expected to bring greater regulatory clarity as the first circRNA therapeutics enter clinical trials and generate human safety and efficacy data. Regulatory agencies are likely to issue draft guidance documents specific to circRNA, addressing topics such as analytical characterization, potency assays, and risk mitigation strategies. The collaborative approach between industry and regulators will be critical to establishing robust approval pathways and accelerating patient access to these innovative therapies.

Intellectual Property and Patent Trends

The intellectual property (IP) landscape for circular RNA (circRNA) therapeutics is rapidly evolving as the field matures and attracts significant investment. In 2025, the number of patent filings related to circRNA technologies continues to rise, reflecting both the growing scientific interest and the commercial potential of this modality. Key areas of patent activity include methods for synthesizing and stabilizing circRNAs, delivery systems, and therapeutic applications targeting a range of diseases, particularly in oncology, rare genetic disorders, and infectious diseases.

Several biotechnology companies are at the forefront of circRNA IP development. Orna Therapeutics, a pioneer in the field, has built a robust patent portfolio covering its proprietary oRNA™ circular RNA platform, which includes innovations in circularization methods, sequence optimization, and delivery technologies. The company’s IP strategy is designed to protect its lead programs in areas such as in vivo protein replacement and cell therapy, and it has publicly disclosed multiple patent applications and granted patents in the US, Europe, and Asia.

Another notable player, Laronde, is developing its Endless RNA™ (eRNA) platform and has filed patents on unique aspects of circRNA design, manufacturing, and therapeutic use. Laronde’s approach emphasizes modularity and scalability, and its IP filings reflect efforts to secure broad claims around the use of circRNAs for durable protein expression in various therapeutic contexts.

In addition to these dedicated circRNA companies, established RNA therapeutics firms such as Moderna and BioNTech have begun to expand their patent portfolios to include circRNA-based technologies, signaling a recognition of the modality’s potential to complement or surpass linear mRNA approaches. These companies are leveraging their experience in mRNA manufacturing and delivery to accelerate circRNA innovation and secure IP positions in this emerging space.

The competitive IP environment is also driving increased collaboration and licensing activity. Universities and research institutes, which hold foundational patents on circRNA biology and engineering, are entering into partnerships with industry players to translate academic discoveries into therapeutic products. This trend is expected to intensify over the next few years as more circRNA candidates advance into clinical development and as regulatory agencies provide clearer guidance on the patentability of novel RNA constructs.

Looking ahead, the circRNA therapeutics sector is likely to see continued growth in patent filings, with a focus on next-generation delivery systems, improved manufacturing processes, and new therapeutic indications. The outcome of ongoing patent disputes and the evolution of global IP frameworks will play a critical role in shaping the competitive landscape and determining which companies will lead the commercialization of circRNA medicines.

Investment, Funding, and M&A Activity

The investment landscape for circular RNA (circRNA) therapeutics is rapidly evolving as the field transitions from early-stage research to clinical and commercial development. In 2025, the sector is witnessing a surge in venture capital, strategic partnerships, and merger and acquisition (M&A) activity, driven by the promise of circRNA’s unique stability, translational efficiency, and potential to address previously undruggable targets.

Several biotechnology companies specializing in circRNA therapeutics have secured significant funding rounds in the past year. Orna Therapeutics, a pioneer in the development of fully engineered circRNA therapies, closed a $221 million Series B financing in 2023, with continued investor interest into 2025 as the company advances its lead oncology and vaccine programs. Orna’s platform has attracted strategic collaborations, most notably a multi-billion dollar partnership with Merck & Co., Inc. (MSD), announced in 2022 and expanded in subsequent years, to co-develop circRNA-based vaccines and therapeutics.

Another key player, Lantern Pharma, has expanded its RNA therapeutics pipeline to include circRNA modalities, leveraging artificial intelligence for target discovery and optimization. The company’s recent capital raises and partnerships with academic institutions underscore the growing confidence in circRNA’s therapeutic potential.

In Europe, Thera-circ (Thera-circ GmbH) has emerged as a notable startup, focusing on circRNA drug discovery for rare diseases and oncology. The company secured seed funding in late 2024 and is actively seeking Series A investment in 2025, reflecting the increasing interest from European venture funds in this modality.

M&A activity is also intensifying as established pharmaceutical companies seek to acquire or partner with circRNA innovators to bolster their RNA therapeutics portfolios. Industry observers anticipate further consolidation in 2025 and beyond, with large pharma companies targeting startups with proprietary circRNA platforms, delivery technologies, or promising preclinical assets. The competitive landscape is further shaped by the entry of major RNA technology players, such as Moderna, Inc., which has publicly signaled interest in expanding beyond mRNA to next-generation RNA modalities, including circRNA.

Looking ahead, the next few years are expected to see continued robust investment, with a focus on clinical translation, manufacturing scale-up, and strategic alliances. The sector’s momentum is underpinned by the first circRNA therapeutics entering clinical trials, which will be a key inflection point for both investor confidence and M&A valuations.

Challenges: Manufacturing, Scalability, and Safety

Circular RNA (circRNA) therapeutics have emerged as a promising modality in the RNA-based drug landscape, but their translation from laboratory to clinic faces significant challenges in manufacturing, scalability, and safety—issues that are particularly pressing as the field moves into 2025 and the years immediately ahead.

One of the foremost challenges is the efficient and reproducible manufacturing of high-purity circRNA molecules at scale. Unlike linear mRNA, circRNAs require precise back-splicing or enzymatic ligation to achieve their covalently closed structure, which is essential for their stability and function. Current manufacturing methods, such as in vitro transcription followed by enzymatic or chemical circularization, often result in heterogeneous products and low yields. Companies like Orna Therapeutics and Lantern Pharma are actively developing proprietary platforms to address these bottlenecks, focusing on scalable enzymatic ligation and purification processes. Orna Therapeutics, for example, has reported advances in producing synthetic circRNAs with improved efficiency, but large-scale, GMP-compliant production remains a work in progress.

Scalability is closely tied to manufacturing. As circRNA therapeutics progress toward clinical trials, the need for robust, reproducible, and cost-effective production becomes critical. The industry is currently investing in automation and closed-system bioprocessing to minimize contamination and batch variability. Moderna, which has expanded its RNA technology portfolio to include circRNA, is leveraging its established mRNA manufacturing infrastructure to explore scalable circRNA production, though the unique requirements of circularization present new technical hurdles.

Safety is another major concern as circRNA therapeutics move closer to human trials. While circRNAs are inherently more stable and less immunogenic than linear RNAs, off-target effects, unintended immune activation, and the persistence of synthetic circRNAs in vivo require thorough investigation. Regulatory agencies are expected to scrutinize these aspects closely, especially as the first clinical candidates enter early-phase trials in 2025 and beyond. Companies are conducting extensive preclinical studies to assess biodistribution, immunogenicity, and long-term safety, with Orna Therapeutics and Lantern Pharma among those leading the charge.

Looking ahead, the next few years will likely see the emergence of standardized manufacturing protocols, improved circularization chemistries, and more sophisticated analytical tools for quality control. Industry collaboration and investment in specialized manufacturing facilities will be crucial to overcoming these challenges and unlocking the full therapeutic potential of circRNAs.

Future Outlook: Opportunities and Market Drivers Through 2030

The future outlook for circular RNA (circRNA) therapeutics through 2030 is marked by significant opportunities and robust market drivers, as the field transitions from early-stage research to clinical and commercial development. As of 2025, circRNA-based therapies are gaining momentum due to their unique structural stability, resistance to exonucleases, and potential for efficient protein translation, which collectively address some of the limitations of linear RNA therapeutics.

A key driver is the increasing investment from both established pharmaceutical companies and specialized biotechnology firms. Orna Therapeutics, a pioneer in the circRNA space, has advanced its proprietary oRNA™ technology platform, focusing on applications in oncology, genetic diseases, and vaccines. In 2022, Orna entered a strategic collaboration with Merck & Co., Inc. (MSD) to develop and commercialize novel circRNA therapies, with the deal valued at up to $3.5 billion in milestones and upfront payments, underscoring the commercial potential and industry confidence in circRNA modalities.

Another notable player, Lantern Pharma, is leveraging artificial intelligence to identify and optimize circRNA candidates for cancer therapeutics, aiming to accelerate the translation of preclinical findings into clinical assets. Meanwhile, EpiVax is exploring circRNA constructs for next-generation vaccines, capitalizing on the platform’s ability to induce robust and durable immune responses.

The market is also buoyed by advances in manufacturing and delivery technologies. Companies such as Precision NanoSystems are developing scalable lipid nanoparticle (LNP) systems tailored for circRNA delivery, addressing a critical bottleneck for clinical translation. These innovations are expected to facilitate the entry of multiple circRNA candidates into early-phase clinical trials by 2026–2027.

Regulatory agencies are increasingly engaging with developers to establish guidelines for circRNA therapeutics, drawing on precedents set by mRNA-based drugs and vaccines. This regulatory clarity is anticipated to streamline the path to market, particularly for indications with high unmet medical need.

Looking ahead to 2030, the circRNA therapeutics market is poised for rapid expansion, driven by the convergence of scientific validation, strategic partnerships, and technological advancements. The first circRNA-based therapies are expected to reach late-stage clinical trials by the late 2020s, with potential approvals in oncology, rare diseases, and infectious disease prevention. As the competitive landscape evolves, collaborations between biotech innovators and large pharmaceutical companies will likely accelerate, further propelling the sector toward commercialization and broader patient impact.

Sources & References

• Merck & Co., Inc.
• Lantern Pharma
• Aaron Pharma
• BioNTech SE
• RiboCure Pharmaceuticals
• Thermo Fisher Scientific
• Evotec SE
• European Medicines Agency
• Laronde