Oligonucleotide Synthesis Market to Hit $44.9 Billion by 2033

Introduction

The Oligonucleotide Synthesis Market is projected to expand significantly, with an expected growth from USD 9.1 billion in 2023 to USD 44.9 billion by 2033, demonstrating a compound annual growth rate of 17.3%. This growth is largely fueled by continuous innovations in genetic and molecular sciences, especially in therapeutic applications.

Advancements in sustainable manufacturing practices are vital to this industry’s evolution. Traditional oligonucleotide synthesis, characterized by the use of hazardous chemicals and high waste production, is undergoing transformation. The industry is shifting towards greener methodologies that reduce environmental impact and enhance efficiency. This transition not only supports sustainable development but also aligns with global environmental sustainability goals.

Technological innovations continue to redefine the oligonucleotide synthesis landscape. The adoption of microchip-based synthesis technologies since the early 1990s has significantly reduced production costs while increasing efficiency. These technologies have broadened oligonucleotide applications in areas such as synthetic biology and genetic engineering, thereby accelerating research and development activities across various scientific domains.

The therapeutic applications of oligonucleotides represent a major growth driver. The use of oligonucleotide drugs, including antagomirs, aptamers, and small interfering RNAs (siRNAs), in clinical treatments of diverse diseases showcases their growing importance. Notably, their role in developing mRNA vaccines during the COVID-19 pandemic has highlighted their potential in medical advancements.

Emerging synthesis methods, such as enzymatic synthesis, offer substantial improvements over traditional chemical synthesis by enabling milder reaction conditions and minimizing environmental impacts. These methods enhance the accuracy and length of oligonucleotides, presenting a promising future for the industry. Additionally, innovations like convergent synthesis improve scalability and cost-effectiveness by reducing impurities and streamlining production processes.

Recent developments further illustrate the market’s dynamism. In January 2024, Integrated DNA Technologies expanded by opening a new facility in Europe to cater to the increasing demand for synthetic oligonucleotides. Thermo Fisher Scientific acquired Bio-Rad’s High Throughput PCR Systems business in October 2023, enhancing its qPCR offerings. Furthermore, Agilent Technologies launched the HaloPlex™ G4 system in August 2023, which utilizes microfluidic technology for advanced gene expression analysis. These strategic moves by key players indicate robust growth and escalating competition within the market.

Key Takeaways

• In 2023, the global oligonucleotide synthesis market was valued at USD 9.1 billion and is projected to grow at a CAGR of 17.3%.
• Oligonucleotide-based drugs comprised 38.1% of the market in 2023, propelled by the increasing demand for targeted therapeutic applications.
• The pharmaceutical and biotechnology sectors dominated, contributing 34.6% to the market’s revenue in 2023.
• Therapeutic applications, particularly for cancer and neurological disorders, are anticipated to significantly drive market growth, representing a 42.2% share.
• North America maintained the largest market share, accounting for 40.2% of the revenue in 2023.
• The Asia-Pacific region is emerging as the fastest-growing market, with significant contributions from Japan and China.
• Thermo Fisher Scientific, Merck & Co., and GE Healthcare are identified as leading players in the oligonucleotide synthesis market.

Oligonucleotide Synthesis Statistics

Synthesis Process and Efficiency

• Oligonucleotides are short strands, usually ranging from 13 to 25 nucleotides, and seldom exceed 200 nucleotides.
• The synthesis process involves adding nucleotides cyclically from the 3′ end to the 5′ end of the chain.
• Each addition cycle has a coupling efficiency of between 98.5% and 99.5%, with higher efficiencies reducing truncated molecules.
• Incomplete reactions and side reactions during synthesis affect the overall efficiency and quality of the final product.

Yield and Purity

• Traditional synthesis methods yielded a median purity of 60%.
• New purification methods have improved median purity to 78%, showing an 18% increase over older methods.
• With the new method, 89% of oligonucleotide products are within a factor of 2 of the median concentration.
• The synthesis of a 140 base pair oligonucleotide with a coupling efficiency of 98.5% results in 90% truncated molecules.
• A coupling efficiency of 99.5% leads to 50% of oligonucleotides being of full length.
• Column-based synthesis offers a coupling failure rate of about 0.5% per event, achieving over 99.5% success per step.

Advancements in Synthesis Techniques

• Single-round chain extension using branched supports shows yields between 75% and nearly 100%.
• Cyclodextrin-supported pentamers reach an average coupling yield of about 85%.
• Manual synthesis on aminomethyl PS resin achieves nearly 100% efficiency, despite a less effective first T coupling at 77%.
• Derivatization of Rink amide PS resin produces tetramers and pentamers with yields of 78% and 85%, respectively.
• New approaches have reduced impurities by up to 40% after 20 or more cycles.

Yield Optimization

• The current yield of oligonucleotide synthesis stands at approximately 55%.
• Scaling up operations from 2 to 600-mmol scales shows comparable outcomes.
• Achieving about 75% yield was possible by omitting the capping step in the synthesis process.
• Increasing the yield to 90% from 55% could potentially reduce the number of synthesis runs by about 90%.

Product Quality Across Manufacturers

• Analysis shows that 97.2% of oligonucleotide molecules were intact across various manufacturers and purity grades.
• The frequency of synthesis errors, like substitutions, is generally low, with a mean error frequency of 0.025% across all types.
• Variability in oligonucleotide molecules with deletions ranges from 0.2% to 11.7%, depending on the type.

Yield for Specific Oligonucleotide Lengths

• Yields for trimer and pentamer oligonucleotides were 77% and 52%, respectively.
• 5-mer oligonucleotides have an approximate 50% overall yield with 75% purity, while 9-mer oligonucleotides have about 40% yield with 49% purity.
• Purity levels increased to over 90% after final purification by ion exchange chromatography.

Emerging Trends

• Biocatalytic Manufacturing Processes: The shift towards biocatalytic methods in oligonucleotide synthesis marks a significant development. These methods are favored for their environmental benefits and efficiency. Unlike traditional chemical synthesis, which often involves hazardous reagents and generates waste, biocatalytic processes use enzymes that are both cleaner and more specific. This green alternative not only aligns with global sustainability goals but also improves the scalability and feasibility of oligonucleotide production.
• Enzymatic Synthesis of RNA Oligonucleotides: There is a growing interest in the enzymatic synthesis of RNA oligonucleotides, driven by the need for precision in therapeutic applications. This method enables the production of RNA molecules with high specificity, which is essential for targeting genetic disorders. The accuracy of enzymatic synthesis allows for the creation of oligonucleotides that can effectively mimic or inhibit natural RNA, making them powerful tools in gene therapy and related medical treatments.
• Innovations in Scale-Up Manufacturing: Advancements in manufacturing technology are pivotal as they facilitate the large-scale production of oligonucleotides. These innovations are crucial for making oligonucleotide-based therapies more accessible and cost-effective. Modern techniques have streamlined traditional processes, integrating multiple synthesis steps into single, efficient operations. This not only speeds up production but also reduces costs, paving the way for broader use in drug development.
• Expansion in Therapeutic Applications: Oligonucleotides are finding roles in a diverse array of therapeutic areas, extending beyond rare genetic disorders to include common conditions such as Alzheimer’s disease. This expansion is indicative of the growing potential of oligonucleotides in medical treatments. As research progresses, the versatility of these molecules opens up new avenues for addressing a wide spectrum of diseases, highlighting their significant impact on modern medicine.
• Targeted Drug Development: The development of oligonucleotide drugs is increasingly focused on targeting specific genetic components of diseases. This approach is particularly evident in the fields of neurodegenerative and cardiovascular diseases. By designing oligonucleotides that can precisely interact with specific genes or regulatory elements within cells, researchers are pushing the boundaries of precision medicine. This trend underscores a strategic shift towards personalized medical therapies that offer targeted, effective treatment options.

Use Cases

• Treatment of Genetic Diseases: Oligonucleotides play a crucial role in the advancement of treatments for genetic disorders by specifically targeting genetic mutations. These synthetic molecules are designed to alter gene expression or correct mutations at the DNA or RNA level. Notable applications include therapies for spinal muscular atrophy and Huntington’s disease, where they can significantly influence disease outcomes by modifying the genetic information that leads to the condition. This precision medicine approach allows for the development of tailored therapies that can potentially halt or reverse the progression of genetic diseases.
• Cancer Therapy Applications: In the realm of oncology, oligonucleotides are employed to suppress the activity of oncogenes or to enhance the immune system’s response to cancer cells. This method of targeted therapy helps to decrease adverse side effects typically associated with traditional cancer treatments while improving the effectiveness of the therapy. By specifically targeting molecular processes that fuel cancer growth, oligonucleotides provide a strategic advantage in cancer management, contributing to more personalized and effective treatment protocols.
• Cardiovascular Therapies: Oligonucleotides are increasingly utilized in cardiovascular treatments, particularly in managing cholesterol levels through targeting specific proteins such as lipoprotein(a). This application is essential in treating hypercholesterolemia, a condition that significantly raises the risk of heart disease. By modulating the genetic factors influencing cholesterol production, oligonucleotides offer a promising avenue for therapeutic intervention, potentially reducing the incidence of cardiovascular events in affected populations.
• Neurological Applications: In neurology, oligonucleotides are used to address disorders of the central nervous system by targeting genes that influence neural function and health. These treatments focus on specific genetic elements involved in disease mechanisms, offering hope for conditions where few treatments currently exist. By manipulating gene expression related to neurological health, oligonucleotides help in developing new therapies that can improve life quality and disease management for patients with chronic neurological conditions.
• Diagnostics and Research: Beyond their therapeutic applications, oligonucleotides are fundamental in diagnostics and biomedical research. They are crucial in crafting assays and experimental tools that enable scientists to diagnose genetic disorders, understand disease pathways, and explore new therapeutic approaches. This versatility makes oligonucleotide synthesis a vital technology in the ongoing quest to understand complex diseases and develop innovative treatments, thereby expanding the boundaries of medical science and clinical practice.

Conclusion

In conclusion, the oligonucleotide synthesis market is on a robust growth trajectory, driven by groundbreaking technological advancements and expanding therapeutic applications. Innovations in sustainable manufacturing and enzymatic synthesis techniques are setting new benchmarks for efficiency and environmental responsibility. As the industry continues to evolve, the increased focus on personalized medicine and the broadening scope of oligonucleotide applications in healthcare are paving the way for significant advancements. The market’s strong growth prospects are supported by strategic investments and expansions by key industry players, ensuring its continued relevance and impact in the biotechnological and pharmaceutical landscapes.

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