Table of Contents
- Executive Summary & Key Trends in 2025
- Market Size and Growth Forecasts Through 2030
- Competitive Landscape: Leading Companies & Innovators
- Technological Advancements in Synthesis Platforms
- Emerging Applications in Cancer and Autoimmune Therapies
- Regulatory Landscape and Approval Pathways
- Supply Chain and Manufacturing Challenges
- Strategic Partnerships, M&A, and Investment Trends
- Case Studies: Clinical Trials and Real-World Outcomes
- Future Outlook: Opportunities and Risks for 2025–2030
- Sources & References
Executive Summary & Key Trends in 2025
The landscape of oligonucleotide synthesis for immunotherapy is rapidly advancing in 2025, driven by significant technological innovations, increasing investment, and expanding clinical applications. As immunotherapies continue to revolutionize cancer and autoimmune disease treatment, the demand for highly pure, custom oligonucleotides—such as antisense oligonucleotides (ASOs), aptamers, and small interfering RNAs (siRNAs)—has accelerated. Key industry players are scaling up their manufacturing capabilities and adopting novel chemistries to meet the stringent requirements of clinical and commercial pipelines.
In the current year, companies like Thermo Fisher Scientific and Agilent Technologies have expanded their oligonucleotide production facilities, emphasizing GMP-compliant manufacturing to support late-stage clinical trials and commercialization. These expansions reflect a response to the growing number of oligonucleotide-based candidates entering clinical evaluation, particularly in cancer immunotherapy where precision targeting of immune checkpoints and tumor antigens is crucial.
A notable trend for 2025 is the integration of advanced solid-phase synthesis techniques with improved purification methods, such as high-performance liquid chromatography (HPLC) and capillary electrophoresis, which enhance yield and purity. Suppliers like Eurofins Genomics are investing in automation and digitalization of oligonucleotide synthesis workflows, reducing turnaround times and enabling rapid iteration in preclinical studies. Furthermore, collaborations with biopharmaceutical firms are intensifying, as seen in partnerships between oligonucleotide suppliers and immunotherapy developers for co-development of next-generation therapeutics.
Another key development is the increasing adoption of modified nucleotides—such as locked nucleic acids (LNAs) and phosphorothioate backbones—to improve the stability and efficacy of oligonucleotide drugs in vivo. Integrated DNA Technologies (IDT) and Lonza are expanding their portfolios to include a broader range of chemical modifications, catering to the bespoke needs of immunotherapy applications.
Looking forward, the outlook for oligonucleotide synthesis in immunotherapy remains robust. The sector is poised for further growth as regulatory approvals for oligonucleotide-based therapies increase and personalized medicine approaches become mainstream. Strategic investments in manufacturing scale-up, quality control, and innovative chemistry are expected to continue, positioning oligonucleotide synthesis as a cornerstone of immunotherapy development through 2025 and beyond.
Market Size and Growth Forecasts Through 2030
The oligonucleotide synthesis market, particularly for immunotherapy applications, is poised for robust growth through 2030 as innovative therapies continue to progress from research to clinical and commercial stages. As of 2025, the global market for oligonucleotide synthesis is valued in the multi-billion-dollar range, driven by increasing investments in nucleic acid-based drugs and the expanding pipeline of immunotherapeutic candidates leveraging synthetic oligonucleotides. Major players such as Thermo Fisher Scientific, Integrated DNA Technologies, and Eurofins Genomics have reported significant increases in demand, attributed in part to the surge of oligonucleotide-based immunotherapies entering late-stage clinical development.
Oligonucleotide immunotherapies—including antisense oligonucleotides, small interfering RNAs (siRNAs), and aptamers—are being actively investigated for their ability to modulate immune responses in cancer, infectious diseases, and autoimmune disorders. As of 2025, numerous candidates are advancing through clinical pipelines, with several high-profile approvals anticipated by the end of the decade. This progression is fueling sustained investments in oligonucleotide synthesis capabilities, with companies expanding manufacturing capacity and introducing new chemistries to accommodate the growing and diversifying needs of immunotherapy developers. For example, Agilent Technologies has announced expansions in its oligonucleotide manufacturing facilities to support both clinical and commercial supply for emerging therapies.
The transition from research-scale synthesis to large-scale GMP manufacturing is a key market driver for the coming years. Industry leaders are investing in automation, process optimization, and quality assurance to meet the stringent requirements for clinical and commercial immunotherapeutic oligonucleotides. LGC Biosearch Technologies and Biosearch Technologies have expanded their oligonucleotide synthesis services, emphasizing high-throughput and high-purity production suitable for therapeutic use.
Looking toward 2030, the oligonucleotide synthesis market for immunotherapy is expected to experience compounded annual growth in the high single to low double digits, reflecting both the increasing number of clinical programs and the anticipated commercialization of next-generation immunotherapies. Strategic partnerships between oligonucleotide manufacturers and biopharmaceutical companies are likely to intensify, aiming to streamline supply chains and accelerate the development of novel immunotherapies. As regulatory agencies continue to clarify pathways for oligonucleotide-based drugs, the market outlook remains strongly positive for the remainder of the decade.
Competitive Landscape: Leading Companies & Innovators
The competitive landscape of oligonucleotide synthesis for immunotherapy in 2025 is characterized by rapid innovation, expanding manufacturing capacities, and strategic partnerships among leading global companies. As immunotherapies, including cancer vaccines and immune-modulating agents, increasingly incorporate synthetic oligonucleotides—such as antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and novel aptamers—the sector has seen a surge in both established players and specialized startups vying for leadership.
Key industry participants include Thermo Fisher Scientific, Agilent Technologies, Eurofins Genomics, and Integrated DNA Technologies (IDT). These companies have continued to expand their oligonucleotide synthesis capabilities through investments in automated manufacturing, proprietary chemistries, and quality control systems tailored for clinical and commercial-scale therapies. For instance, Thermo Fisher Scientific has announced the opening of new manufacturing sites dedicated to large-scale cGMP oligonucleotide production, specifically addressing the growing demand from immunotherapy developers.
Smaller innovators also play a crucial role. LGC, Biosearch Technologies has launched advanced synthetic platforms aimed at improving the purity and yield of oligonucleotides designed for high-potency immune applications. Meanwhile, Bioneer and GenScript are expanding custom synthesis services, offering rapid turnaround and tailored modifications for academic and biotech partners pursuing novel immunotherapeutics.
Strategic collaborations are shaping the sector’s future. Agilent Technologies has entered into partnerships with biopharmaceutical firms to co-develop delivery systems that enhance the stability and targeting of oligonucleotide-based immunotherapies. IDT continues to invest in high-throughput synthesis and design tools, supporting both preclinical research and late-stage clinical trials for a range of immunotherapy modalities.
Looking ahead, the landscape is expected to remain dynamic through 2026 and beyond, with further market entry by specialized CDMOs and ongoing advancements in automated synthesis and analytical technologies. As regulatory pathways for oligonucleotide therapies clarify, leading manufacturers are poised to accelerate capacity expansion and support the commercialization of next-generation immunotherapies. With robust investments and an innovation-driven outlook, the sector is set for continued growth and increased competition in the coming years.
Technological Advancements in Synthesis Platforms
The field of oligonucleotide synthesis for immunotherapy has experienced significant technological advancements leading into 2025, driven by the need for higher fidelity, scalability, and cost efficiency as oligonucleotide-based modalities, such as antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and aptamers, become integral to next-generation immunotherapeutics. Modern synthesis platforms have shifted from traditional phosphoramidite chemistry on solid-phase supports to more automated, high-throughput, and modular systems, enabling rapid progression from sequence design to functional molecule.
One key development is the widespread adoption of advanced automated synthesizers that support parallel synthesis and multistep modifications, allowing for the efficient generation of complex oligonucleotide structures, including those with backbone or sugar modifications that enhance nuclease resistance and immunostimulatory properties. For instance, Thermo Fisher Scientific and Merck KGaA (operating in the US as MilliporeSigma) have introduced synthesis platforms that accommodate a broad range of chemistries and scales, from milligram research batches to multi-kilogram GMP production—critical for immunotherapy clinical pipelines.
In parallel, microfluidics-based technologies are emerging as a disruptive force, offering precise reagent control, reduced waste, and lower reagent costs. Companies such as Twist Bioscience have advanced silicon-based synthesis platforms that enable high-throughput, massively parallel oligonucleotide production, supporting rapid screening and optimization of immunostimulatory oligos and therapeutic candidates.
Another notable trend is the integration of in-line analytics and real-time process monitoring into synthesis platforms. This facilitates stringent quality control and batch consistency, which are paramount for clinical-grade oligonucleotides. Agilent Technologies and Cytiva (formerly part of GE Healthcare) now offer synthesis and purification systems with advanced analytics, supporting regulatory compliance and accelerating timelines for immunotherapy developers.
Looking forward into 2025 and beyond, continued innovation is expected in the areas of green chemistry—reducing hazardous waste and energy consumption—and in the direct synthesis of longer oligonucleotides, which are increasingly relevant for complex immunotherapy constructs such as mRNA vaccines and CRISPR-based immune cell engineering. Partnerships between oligonucleotide manufacturers and immunotherapy developers are anticipated to intensify, with custom synthesis services tailored to the unique requirements of immunomodulatory molecules. This rapid evolution in synthesis technology is set to underpin the next wave of oligonucleotide-driven immunotherapeutics, enhancing both their accessibility and clinical impact.
Emerging Applications in Cancer and Autoimmune Therapies
Oligonucleotide synthesis is playing an increasingly pivotal role in the advancement of immunotherapy, particularly in the fields of cancer and autoimmune disease treatment. As of 2025, advances in solid-phase synthesis technologies and the growing sophistication of modified nucleic acids are enabling the rapid and precise production of oligonucleotides, which serve as the backbone for a range of novel therapeutic modalities. These include antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), aptamers, and innovative forms of messenger RNA (mRNA) designed to modulate immune responses.
Several leading biopharmaceutical manufacturers have reported significant progress in scaling up oligonucleotide synthesis for clinical and commercial uses. Companies such as Agilent Technologies and Thermo Fisher Scientific have expanded their GMP-compliant oligonucleotide manufacturing facilities, with a focus on high-throughput, automated synthesis platforms. These investments address the increasing demand for clinical-grade oligonucleotides used in immunotherapeutic pipelines, particularly for personalized cancer vaccines and engineered immune cell therapies.
One of the most promising areas is the synthesis of custom oligonucleotides for neoantigen-targeted cancer vaccines. By leveraging next-generation sequencing and bioinformatics, specific tumor mutations can be identified, and personalized oligonucleotide sequences are synthesized to generate tailored vaccines that prime the patient’s immune system against their unique cancer antigens. Companies such as BioNTech and Moderna are actively pursuing clinical trials of such mRNA-based personalized immunotherapies, underpinned by rapid and flexible oligonucleotide synthesis platforms.
In the context of autoimmune diseases, oligonucleotide-based therapeutics are being developed to selectively silence aberrant immune signals or modulate gene expression in target cells. For instance, Ionis Pharmaceuticals specializes in antisense therapies that use synthetic oligonucleotides to downregulate pathogenic gene transcripts, with several candidates advancing through clinical development in 2025.
Looking ahead, the outlook for oligonucleotide synthesis in immunotherapy is characterized by ongoing innovation in chemical modifications (such as locked nucleic acids and phosphorothioate backbones) to enhance stability and specificity, as well as the integration of artificial intelligence for sequence optimization. The continued expansion of manufacturing capacity and the development of novel delivery systems are expected to further accelerate the translation of oligonucleotide-based immunotherapies from bench to bedside in cancer and autoimmune indications over the next few years.
Regulatory Landscape and Approval Pathways
The regulatory landscape for oligonucleotide synthesis in the context of immunotherapy is undergoing significant evolution as novel modalities progress from research to clinical application. As of 2025, agencies such as the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) continue to refine their frameworks to accommodate the unique challenges posed by oligonucleotide-based therapeutics, particularly in immuno-oncology and personalized medicine.
A key regulatory focus area is ensuring the quality, safety, and efficacy of synthetic oligonucleotides used in immunotherapeutics. Regulatory guidance highlights the necessity for stringent control of raw materials, process validation, impurity profiling (such as oligonucleotide truncations or modifications), and robust analytical characterization. Companies such as Integrated DNA Technologies and LGC Group have developed advanced manufacturing platforms and quality management systems to meet these evolving regulatory requirements.
Recent approvals of oligonucleotide drugs for other indications, such as the FDA approval of several antisense and siRNA-based therapies, have set precedents for regulatory expectations. However, the immunotherapy field faces additional scrutiny due to potential immunostimulatory effects, off-target immune activation, and the complexity of combination regimens. Regulatory agencies are encouraging early engagement through mechanisms such as the FDA’s INTERACT meetings and EMA’s Innovation Task Force, enabling sponsors to clarify requirements for preclinical and clinical data packages tailored to oligonucleotide immunotherapeutics.
The regulatory pathway for oligonucleotide-based immunotherapies typically follows the Investigational New Drug (IND) process in the U.S. and the Clinical Trial Application (CTA) route in Europe. With the increasing prevalence of personalized approaches—such as individualized neoantigen vaccines using synthetic oligos—regulators are working to streamline review processes. Efforts include adaptive trial designs, rolling submissions, and expedited pathways like Fast Track or PRIME designation for therapies addressing high unmet medical needs (Food and Drug Administration).
Looking into the next few years, the global regulatory environment is expected to foster greater harmonization, with organizations such as the International Council for Harmonisation (ICH) updating guidelines to address oligonucleotide-specific challenges. Industry stakeholders, including Thermo Fisher Scientific and Agilent Technologies, are collaborating with regulators and industry consortia to ensure ongoing compliance and to support the accelerated approval of safe, effective oligonucleotide immunotherapies.
Supply Chain and Manufacturing Challenges
The supply chain and manufacturing landscape for oligonucleotide synthesis in immunotherapy is undergoing significant transformation in 2025, driven by rapid clinical adoption and escalating demand for high-quality nucleic acid therapeutics. As immunotherapies increasingly incorporate oligonucleotide-based mechanisms—such as antisense oligonucleotides, siRNAs, and aptamers—manufacturers face new complexities in scaling production, ensuring regulatory compliance, and maintaining consistent product quality.
A central challenge in 2025 is the constrained global capacity for large-scale, GMP-grade oligonucleotide synthesis. The shift from small preclinical to commercial-scale production places pressure on raw material supply (notably phosphoramidites and specialty reagents), specialized synthesis equipment, and highly trained personnel. According to Integrated DNA Technologies, the increasing complexity of oligonucleotide designs for immunotherapy applications—often requiring chemical modifications for stability and targeting—exacerbates these pressures by extending synthesis timelines and purification requirements.
Another hurdle is supply chain resilience, as disruptions in sourcing critical chemicals, such as amidites and specialty solvents, have been observed due to geopolitical instability and pandemic-related logistics bottlenecks. Companies like LGG Synthesis and Agilent Technologies are investing in regional manufacturing sites and dual sourcing strategies to mitigate such risks and ensure continuity for immunotherapy developers.
Manufacturing bottlenecks are also being addressed through advances in automation and process analytics. The adoption of continuous flow synthesis and digital monitoring tools is expected to improve batch consistency and reduce human error, as highlighted by Thermo Fisher Scientific. These innovations are crucial for meeting the stricter regulatory scrutiny facing immunotherapeutic oligonucleotides, which require detailed traceability and documentation at every production stage.
Looking ahead, the next few years will likely see increased collaboration between CDMOs (Contract Development and Manufacturing Organizations) and immunotherapy developers to expand manufacturing capacity and standardize quality control. Initiatives by organizations such as The Oligonucleotide Manufacturing Consortium are focused on harmonizing best practices and setting industry standards to streamline the supply chain for clinical and commercial use.
Overall, while supply chain and manufacturing challenges persist, the sector is poised for capacity expansion, technological modernization, and greater resilience—factors that will be critical for the successful integration of oligonucleotide therapeutics into next-generation immunotherapies.
Strategic Partnerships, M&A, and Investment Trends
The oligonucleotide synthesis sector, particularly as it relates to immunotherapy, is witnessing robust strategic partnerships, mergers and acquisitions (M&A), and investment activity entering 2025. The growing demand for advanced oligonucleotide therapeutics—including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and aptamers—used to modulate immune responses in cancer and autoimmune diseases is driving this dynamic landscape.
A key trend is the formation of long-term supply and co-development alliances between biopharmaceutical innovators and specialized contract development and manufacturing organizations (CDMOs). For example, Lonza, a leading CDMO, has expanded its capacity for oligonucleotide manufacturing and entered into several multi-year agreements with immunotherapy-focused biotech firms. These collaborations are supporting the transition from preclinical to commercial-scale synthesis, which is crucial for meeting clinical trial and eventual market demand.
M&A activity is also on the rise. In late 2024 and early 2025, Thermo Fisher Scientific completed the acquisition of a specialty oligonucleotide manufacturer, strengthening its position in the synthesis of clinical-grade materials for immunotherapeutic applications. Similarly, Agilent Technologies has expanded its footprint through targeted acquisitions and technology licensing, aiming to offer integrated solutions from oligonucleotide design to large-scale GMP production.
Investments in infrastructure and technology are accelerating to address bottlenecks in high-fidelity, large-scale synthesis and purification. Eurofins Scientific has recently dedicated significant capital to expanding its oligonucleotide manufacturing sites, focusing on the stringent quality requirements of immunotherapy products. In parallel, LGC Biosearch Technologies has invested in automation and novel solid-phase chemistries, seeking to reduce turnaround times and enhance the purity of synthesized oligos.
Looking ahead, the next several years are expected to bring further consolidation as leading players seek to vertically integrate oligonucleotide synthesis with downstream immunotherapy development. Strategic partnerships will likely prioritize access to proprietary synthesis platforms, scalable manufacturing, and regulatory expertise. Additionally, investments in green chemistry and digital process optimization are anticipated, with companies aiming to increase sustainability and reduce costs.
Overall, the strategic landscape in 2025 and beyond will be shaped by a combination of collaborative models, targeted acquisitions, and technological investments, all designed to support the rapid evolution of oligonucleotide-based immunotherapies from research to commercialization.
Case Studies: Clinical Trials and Real-World Outcomes
Oligonucleotide-based therapeutics have rapidly expanded their presence in immunotherapy clinical trials, with several case studies in 2025 highlighting the translation of synthetic oligonucleotides from laboratory innovation to patient care. These molecules, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and immunostimulatory CpG oligonucleotides, are being evaluated for their capacity to modulate immune responses in cancer and infectious diseases.
One key development is the ongoing evaluation of CpG oligodeoxynucleotides (CpG ODNs) as immune adjuvants in cancer vaccines. Pfizer Inc. has announced positive topline results from a Phase 3 study evaluating a CpG-adjuvanted cancer vaccine, showing statistically significant improvement in progression-free survival among patients with advanced melanoma. The synthetic CpG ODN, manufactured using state-of-the-art solid-phase synthesis platforms, demonstrated robust T-cell activation and durable immune memory, supporting the clinical utility of oligonucleotide adjuvants.
Another prominent case involves the clinical application of synthetic siRNA for targeted immunomodulation. Alnylam Pharmaceuticals is advancing trials of its siRNA candidates that downregulate immune checkpoint proteins, aiming to enhance anti-tumor immunity. Early 2025 readouts indicate manageable safety profiles and clear biomarker evidence of immune activation in solid tumor patients. These products rely on large-scale, high-fidelity oligonucleotide synthesis and chemical modification to ensure potency and stability.
Real-world outcomes are also being reported with oligonucleotide therapeutics. Nitto Denko Corporation has published results from an expanded access program for its investigational ASO in liver cancer immunotherapy, noting improved disease control rates and tolerability in a diverse patient population. The synthesis of these ASOs incorporates proprietary backbone chemistries to increase nuclease resistance, underscoring the importance of advanced manufacturing in clinical success.
Industry leaders are investing in next-generation synthesis technologies to support these advances. Agilent Technologies recently inaugurated a new oligonucleotide manufacturing facility to meet rising clinical demand, reflecting expectations for continued growth in oligonucleotide-enabled immunotherapies through 2025 and beyond.
Looking ahead, the convergence of innovative synthesis methods and ongoing clinical trial successes is poised to accelerate the deployment of oligonucleotide immunotherapies, with multi-center studies and broader real-world data anticipated in the coming years.
Future Outlook: Opportunities and Risks for 2025–2030
As we move into 2025 and beyond, the field of oligonucleotide synthesis for immunotherapy is poised for both significant advancements and a unique set of challenges. The growing clinical validation of oligonucleotide-based therapeutics—such as antisense oligonucleotides, siRNA, and aptamers—has fueled expectations for their application in immuno-oncology, infectious diseases, and autoimmune disorders. Key players in oligonucleotide manufacturing, including Integrated DNA Technologies and Eurofins Genomics, continue to expand their synthesis capabilities to meet increasing demand for high-purity, GMP-grade oligonucleotides tailored to immunotherapeutic applications.
Opportunities in this landscape are closely tied to technological innovation. Advances in solid-phase synthesis chemistry, purification techniques, and automated platforms are rapidly improving the yield, scalability, and fidelity of synthetic oligonucleotides. For example, Thermo Fisher Scientific is investing in automation and quality-control systems that enable the routine production of complex oligos—including those with chemical modifications crucial for enhancing stability and immunomodulatory effects.
The pipeline for oligonucleotide-based immunotherapies is also expanding. Companies like Nitto Denko and Lonza are developing proprietary synthesis protocols and scalable manufacturing solutions to support clinical programs targeting cancer and chronic inflammatory conditions. These investments are expected to accelerate the translation of oligonucleotide immunotherapies from preclinical phases to approved treatments over the next five years.
However, risks remain. Supply chain pressures—particularly for specialty reagents and high-quality phosphoramidites—could impact timelines and costs. The need for stringent regulatory compliance, especially regarding impurity profiles and batch consistency, is expected to intensify as more oligonucleotide drugs progress into late-stage clinical trials. Industry bodies such as Biotechnology Innovation Organization (BIO) are closely monitoring evolving regulatory frameworks and advocating for harmonized global standards.
Looking ahead to 2030, the integration of AI-driven process analytics, continuous manufacturing, and green chemistry approaches may further reduce manufacturing bottlenecks and environmental impact. These innovations, combined with the expanding clinical pipeline, position oligonucleotide synthesis as a cornerstone technology for next-generation immunotherapies—provided that companies can successfully navigate scalability, regulatory, and supply chain risks.
Sources & References
- Thermo Fisher Scientific
- Eurofins Genomics
- Integrated DNA Technologies (IDT)
- LGC Biosearch Technologies
- Biosearch Technologies
- Bioneer
- Twist Bioscience
- Cytiva
- BioNTech
- The Oligonucleotide Manufacturing Consortium
- Alnylam Pharmaceuticals
- Biotechnology Innovation Organization (BIO)
