Oligonucleotide Therapeutics for Prevalent Diseases: Scaling Up to Meet Global Demand

As oligonucleotide-based drugs expand beyond rare disease treatments, they’re starting to play a larger role in tackling common and chronic illnesses. From cardiovascular conditions to cancer and inflammatory diseases, these molecules offer targeted, gene-level intervention — but treating widespread populations brings a new challenge: manufacturing at scale.

In this blog, we’ll look at how oligonucleotides are being used to treat prevalent diseases and explore the manufacturing innovations that are making large-scale production viable.

The Expanding Role of Oligonucleotides in Treating Common Conditions

Oligonucleotides — short sequences of DNA or RNA — are designed to bind with specific genetic targets, allowing researchers to silence, modify, or correct gene expression. While they’ve seen success in rare disease treatments, more pharmaceutical companies are now focusing on their potential in more common conditions.

Here are a few areas where oligonucleotide therapeutics are gaining traction:

● Cardiovascular Disease: ASOs targeting PCSK9 or ApoC3 can help reduce harmful cholesterol levels — offering an alternative to traditional statins.
● Liver Disease: GalNAc-conjugated oligonucleotides can deliver precise therapies for non-alcoholic fatty liver disease (NAFLD) and hepatitis.
● Cancer: siRNA therapies can target tumour-specific genes, while aptamers are being developed to guide chemotherapy directly to cancer cells.
● Inflammatory & Autoimmune Conditions: Research is ongoing into oligonucleotides that regulate immune responses in conditions like IBD or rheumatoid arthritis.

As these therapies move into late-stage trials and commercial use, the pressure is on to shift from small, clinical-scale batches to reliable large-scale manufacturing.

Overcoming Manufacturing Barriers Through Scalable Innovation

Unlike highly personalised therapies, treatments for prevalent diseases require volume, consistency, and cost-efficiency. But traditional oligonucleotide synthesis methods — particularly solid-phase synthesis — often struggle to deliver this at scale.

This is where Exactmer’s innovations make a meaningful impact.

Our Nanostar Sieving™ and liquid-phase synthesis platforms are designed for robust, scalable production of complex molecules, helping pharmaceutical companies move from lab to market more efficiently.

How Exactmer’s Technology Supports Scalable Oligo Manufacturing

● Scalability: Our systems can flex from pilot-scale to commercial-scale production without compromising quality — ideal for high-demand treatments.
● Sustainability: We use green chemistries and reduce solvent consumption, helping partners meet environmental and regulatory expectations.
● Process Efficiency: By optimising material usage and improving process mass intensity (PMI), we make large-scale production more economically and operationally viable.

Whether you’re manufacturing an oligo-based cholesterol drug or a therapy for inflammatory conditions, our platform gives you the flexibility and performance needed to keep pace with demand.

Ready to Scale Up Your Oligonucleotide Therapeutic?

As oligonucleotide drugs move into broader markets, the need for reliable, scalable, and sustainable manufacturing grows. At Exactmer, we’ve built technologies to support this evolution — enabling companies to deliver high-quality therapeutics to more patients, more efficiently. Get in touch with us today to see how Exactmer can support your journey from discovery to commercial delivery.

What Are Oligonucleotides and Their Pharmaceutical Applications?

Oligonucleotides have become a cornerstone of modern pharmaceutical research and drug development. These short strands of nucleotides—DNA or RNA molecules—are used in a range of medical applications, from genetic diagnostics to groundbreaking therapies. But what exactly are oligonucleotides, and why are they so crucial in pharmaceuticals?

We’ll break down their structure, synthesis, and expanding role in medicine, along with the manufacturing innovations driving their commercial success.

 

What Are Oligonucleotides?

Oligonucleotides are short sequences of nucleotides—the building blocks of DNA and RNA. Typically consisting of 10 to 50 bases, they can be designed to bind to specific genetic sequences, making them valuable tools in research and therapeutics.

 

There are several types of oligonucleotides, each with unique applications:

● Antisense Oligonucleotides (ASOs) – Bind to messenger RNA (mRNA) to block the production of disease-related proteins.
● Small Interfering RNA (siRNA) – Triggers the degradation of specific mRNA molecules to silence genes.
● Aptamers – Fold into three-dimensional structures that bind to target proteins, functioning similarly to antibodies.
● Primer Oligonucleotides – Essential for DNA amplification in techniques like PCR (Polymerase Chain Reaction).

 

Oligonucleotides are widely used in molecular biology and diagnostics, but their real potential lies in therapeutic applications.

 

Pharmaceutical Applications of Oligonucleotides

1. Genetic Medicine and Rare Disease Treatments

Oligonucleotides have revolutionised the treatment of genetic disorders by offering a way to directly target and modify disease-causing genes.

 

Notable examples include:

● Spinraza (nusinersen) – An ASO used to treat spinal muscular atrophy by modifying gene expression.
● Exondys 51 (eteplirsen) – A therapy for Duchenne muscular dystrophy that promotes the production of functional dystrophin protein.

 

These treatments demonstrate how oligonucleotides can correct genetic defects at the source, paving the way for personalised medicine.

 

2. Cancer Therapies

Oligonucleotide-based drugs are being developed to target specific cancer-related genes, either by silencing oncogenes or enhancing tumour-suppressor activity. Some therapies also use aptamers to bind to cancer cells, helping to deliver chemotherapy drugs more precisely.

 

3. Infectious Disease Treatments

With the rise of viral threats, oligonucleotide therapeutics have gained attention for their potential in antiviral treatments. siRNA-based drugs, for example, can suppress viral replication by targeting viral RNA. Research is ongoing for diseases like hepatitis, HIV, and even emerging viral infections.

 

4. Vaccines and Immune Modulation

Synthetic oligonucleotides can stimulate immune responses, making them valuable in vaccine development. Some DNA and RNA-based vaccines rely on oligonucleotide sequences to prompt an immune reaction against pathogens.

 

5. Neurological Disorders

Conditions like Huntington’s disease and amyotrophic lateral sclerosis (ALS) are being studied for oligonucleotide-based interventions. By targeting the genetic mechanisms behind these diseases, researchers hope to slow or even halt their progression.

 

Challenges in Oligonucleotide Manufacturing

Despite their potential, oligonucleotide-based drugs face manufacturing challenges, particularly in achieving high purity, yield, and scalability. Traditional solid-phase synthesis methods can be inefficient and costly when scaled up for commercial production.

 

This is where Exactmer’s Nanostar Sieving™ and liquid-phase synthesis come in. These advanced technologies streamline oligonucleotide production by improving:

● Scalability – Enabling large-scale manufacturing while maintaining consistency and quality.
● Sustainability – Utilising green chemistries and reducing solvent use to minimise environmental impact.
● Process Efficiency – Optimising material usage to reduce waste and improve process mass intensity (PMI).

 

By overcoming traditional bottlenecks, Exactmer’s innovations are helping to accelerate the commercialisation of oligonucleotide therapeutics.

 

Final Thoughts

Oligonucleotides are transforming medicine, offering targeted therapies for genetic disorders, cancer, and infectious diseases. As their pharmaceutical applications expand, innovations in synthesis and manufacturing will be key to making these therapies widely accessible. To learn more about how our technology can support your oligonucleotide needs, get in touch with us today.

 

Exactmer is at the forefront of this evolution, providing cutting-edge solutions for high-purity, scalable oligonucleotide production.

Solid-Phase vs. Liquid-Phase Oligonucleotide Synthesis: Which is the Future?

Oligonucleotide synthesis has long relied on solid-phase synthesis, a well-established method that has been the industry standard for decades. However, as demand for oligonucleotides continues to rise—particularly in therapeutics and research—manufacturers are seeking more scalable, cost-effective, and sustainable solutions.

Enter liquid-phase synthesis, an emerging alternative that is showing promise for large-scale production. But how do these two methods compare, and is liquid-phase synthesis the future of oligonucleotide manufacturing? Let’s break it down.

 

1. Solid-Phase Oligonucleotide Synthesis: The Industry Standard

How It Works:

Solid-phase synthesis involves attaching nucleotides to a solid support (typically a resin bead) and building the oligonucleotide step by step through chemical reactions. Once the synthesis is complete, the final product is cleaved from the support, purified, and processed.

 

Strengths of Solid-Phase Synthesis:

✓ High efficiency for short oligonucleotides – Ideal for research and diagnostic applications.
✓ Established process – Widely used in the biotech industry, with well-developed protocols.

 

Limitations of Solid-Phase Synthesis:

✖️ Scalability issues – The process becomes inefficient and costly when producing large amounts.
✖️ High reagent consumption – Significant waste is generated, leading to higher Process Mass Intensity (PMI).
✖️ Limited sequence length – Producing longer, more complex oligonucleotides is challenging.

 

2. Liquid-Phase Oligonucleotide Synthesis: A Game-Changer?

How It Works:

Liquid-phase synthesis eliminates the need for a solid support. Instead, oligonucleotides are synthesised in solution, allowing for more flexibility in reaction conditions, purification, and product recovery.

 

Advantages of Liquid-Phase Synthesis:

✓ Better scalability – Easier to scale up for commercial production.
✓ Higher purity and yield – More controlled reactions lead to fewer side products.
✓ Lower reagent consumption – Reduces PMI, making the process more sustainable and cost-effective.
✓ Compatible with advanced purification methods – Technologies like Nanostar Sieving improve efficiency and product quality.

 

Challenges of Liquid-Phase Synthesis:

✖️ Requires specialised expertise – Unlike solid-phase synthesis, liquid-phase processes are still evolving.
✖️ Equipment investment – Companies need to invest in new technologies to transition from solid-phase methods.

 

3. The Future of Oligonucleotide Synthesis: Why Liquid-Phase is Gaining Ground

While solid-phase synthesis has served the industry well, it struggles to keep up with growing commercial demand. The biotech sector is moving toward larger-scale production, making efficiency, cost, and sustainability more important than ever.

This is where Exactmer’s innovations in liquid-phase synthesis, particularly Nanostar Sieving, are changing the game. By addressing scalability, purity, and sustainability, liquid-phase synthesis is positioning itself as the future of oligonucleotide manufacturing.

 

Key Takeaways:

✓ For small-scale research applications, solid-phase synthesis remains practical.
✓ For large-scale therapeutic and commercial oligonucleotide production, Liquid phase shows promise in offering improved efficiency.
✓ Innovations like Nanostar Sieving are making liquid-phase synthesis a viable, cost-effective alternative.

 

Final Thoughts

As demand for oligonucleotides continues to rise, the limitations of solid-phase synthesis are becoming increasingly apparent. Liquid-phase synthesis is emerging as the next step forward, offering a more scalable, cost-effective, and environmentally friendly approach.

At Exactmer, we are leading this transformation with our Nanostar Sieving and liquid-phase synthesis technologies, helping manufacturers achieve higher efficiency and lower PMI.

 

Want to learn more about how Exactmer’s innovations can optimise your oligonucleotide synthesis? Get in touch with us today.

The Challenges of Oligonucleotide Synthesis: Addressing Key Hurdles in Biotechnology

Oligonucleotide synthesis plays a vital role in modern biotechnology, enabling advancements in genetic research, diagnostics, and drug development. As demand for these molecules increases, so too do the challenges in ensuring their quality, scalability, and cost-effectiveness. In this blog, we will explore the main hurdles in oligonucleotide synthesis and highlight the innovations that are helping to overcome them.

 

1. Sequence Complexity and Synthesis Accuracy

One of the most significant challenges in oligonucleotide synthesis is dealing with sequence complexity. The longer and more intricate the sequence, the more prone it is to errors. For example, repetitive sequences, palindromic motifs, or sequences that contain high GC content are notoriously difficult to synthesise. These complexities can lead to inaccuracies during the synthesis process, resulting in incomplete or incorrect sequences that require additional purification steps to achieve the desired product.

Innovation Solutions: Advances like Exactmer’s Nanostar Sieving and liquid-phase synthesis have made significant strides in improving synthesis accuracy by minimising errors in the synthesis process, ensuring more reliable outputs.

 

2. Purity and Yield

Achieving the desired purity and yield is crucial for the effectiveness of oligonucleotides, especially in therapeutic applications. The synthesis of high-quality oligonucleotides often involves side reactions and incomplete sequences, leading to impurities that can affect the performance of the final product. This is particularly problematic when scaling up synthesis for commercial production, where the consistency and reliability of each batch are critical.

Tackling the Issue: Innovations in purification processes and the use of solid-phase synthesis have helped increase the purity of oligonucleotides. Technologies such as Nanostar Sieving aid in better separation and purification, while liquid-phase synthesis offers a streamlined approach to reduce waste and minimise side reactions, ultimately improving yield.

 

3. Scalability of Production

While small-scale oligonucleotide synthesis is relatively straightforward, scaling up production to meet the needs of commercial demand presents unique challenges. To produce large quantities efficiently, manufacturers must ensure that the quality and consistency of each batch remain intact. This often requires the development of advanced equipment and methods that can handle larger volumes without compromising quality.

Innovative Solutions: To meet this demand, companies like Exactmer have focused on optimising the manufacturing process using techniques that improve scalability. By incorporating automated synthesisers and advanced monitoring techniques, production can be scaled up while maintaining high standards of quality and reducing costs.

 

4. Process Mass Intensity (PMI)

Process Mass Intensity (PMI) is a critical metric in the oligonucleotide synthesis process. It measures the amount of raw materials used to produce a unit of product. In other words, PMI helps manufacturers assess the environmental and cost impact of their production processes. A lower PMI indicates a more efficient and sustainable production process, reducing material waste and improving cost-effectiveness.

Why PMI Matters: PMI is essential for optimising the overall efficiency of oligonucleotide production, especially as demand for these molecules grows. Manufacturers must focus on reducing PMI without sacrificing product quality or performance. Innovations such as Nanostar Sieving and liquid-phase synthesis can significantly reduce PMI by streamlining processes and reducing the number of reagents required for production.

 

5. Regulatory and Quality Control Challenges

Given the critical role of oligonucleotides in therapeutic applications, stringent regulatory standards are required to ensure that the final products meet safety and efficacy requirements. Achieving compliance with these regulations while maintaining consistent production quality is an ongoing challenge for manufacturers. Regular quality control checks must be performed at every stage of the synthesis process to ensure that impurities are minimised and that the product is safe for use.

Meeting Regulatory Requirements: Continuous innovation in process monitoring and improvement technologies, along with automated quality control systems, has helped manufacturers comply with regulatory standards while maintaining high production quality. By continuously tracking key synthesis parameters such as temperature, reagent quality, and reaction time, companies can identify potential issues early, minimising the risk of non-compliance.

 

Overcoming the Challenges of Oligonucleotide Synthesis

Oligonucleotide synthesis faces several challenges, from sequence complexity and purification issues to scalability and regulatory requirements. However, ongoing innovations in synthesis technology, such as Exactmer’s Nanostar Sieving and liquid-phase synthesis, are addressing these hurdles head-on. By focusing on optimising production processes, reducing waste, and ensuring high-quality outcomes, the biotechnology industry is poised to meet the growing demand for oligonucleotides in both research and therapeutic applications.

At Exactmer, we are committed to providing cutting-edge solutions that enhance oligonucleotide synthesis, helping our clients navigate the complexities of this critical field. To learn more about how our innovations can assist you in your oligonucleotide synthesis needs, contact us today.

The Growing Demand for Oligonucleotide Synthesis: Uses, Challenges, and Future Opportunities

Oligonucleotide synthesis has emerged as a cornerstone of modern biotechnology, with applications spanning from drug development to genetic research. As demand grows for more personalised treatments and advanced therapies, the role of oligonucleotides in the pharmaceutical and biotech industries becomes increasingly important. In this blog, we’ll explore the various uses of oligonucleotides, the challenges in their synthesis, and the market demand driving their growth. Additionally, we’ll discuss the importance of Process Mass Intensity (PMI) in ensuring high-quality oligonucleotide production.

 

1. Key Uses of Oligonucleotides

Oligonucleotides, short strands of nucleic acids, have become vital tools in both research and medicine. These versatile molecules are used in a wide range of applications, from genetic testing to drug development.

• Diagnostics and Research: Oligonucleotides are central to diagnostic tools such as PCR (Polymerase Chain Reaction), which amplifies DNA for the detection of genetic conditions and infectious diseases. They also play a role in RNA interference, where they help silence specific genes, paving the way for targeted therapies.
• Gene Therapy: In the realm of personalised medicine, oligonucleotides are used to develop therapies that can target and repair specific genetic mutations, offering hope for conditions previously considered untreatable.
• Drug Development: The application of oligonucleotides in the development of antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) has led to new classes of drugs aimed at treating conditions such as Duchenne muscular dystrophy and genetic disorders.

 

2. Challenges in Oligonucleotide Synthesis

Despite their vast potential, the synthesis of oligonucleotides presents several challenges that can affect both the quality and cost of production.

• Sequence Complexity: Longer oligonucleotides or those with repetitive sequences are harder to synthesise. These sequences are prone to errors, requiring additional purification steps to ensure high-quality products.
• Purity and Yield: Achieving the desired purity and yield is a constant challenge. Impurities can arise from incomplete sequences or side reactions during the synthesis process, which can compromise the effectiveness of the final product.
• Scalability: While small-scale synthesis is relatively straightforward, scaling up production to meet commercial demand requires advanced techniques and equipment to ensure consistency across larger batches.

 

However, ongoing innovations in oligonucleotide synthesis technology, such as Exactmer’s Nanostar Sieving and liquid-phase synthesis, are transforming the landscape. These cutting-edge methods address traditional challenges by enhancing scalability, improving purity, and reducing production costs. Nanostar sieving ensures precise separation of desired molecules, while liquid-phase synthesis streamlines the process, minimising errors and waste. These advancements are paving the way for more efficient and reliable large-scale production, meeting the growing demand in research and therapeutic applications.

 

3. Current Commercially Available Oligonucleotide Drugs

The therapeutic potential of oligonucleotides has already been realised with the approval of several commercially available drugs. These treatments are not only revolutionising the pharmaceutical landscape but are also driving the demand for oligonucleotide synthesis.

• Spinraza (nusinersen): This drug, used to treat spinal muscular atrophy, is one of the first antisense oligonucleotide-based drugs to gain FDA approval. Spinraza works by modifying the splicing of the SMN2 gene to increase the production of survival motor neuron protein.
• Exondys 51 (eteplirsen): Approved for the treatment of Duchenne muscular dystrophy, Exondys 51 is another antisense oligonucleotide therapy that targets a specific exon of the dystrophin gene to allow for the production of a functional protein.

 

These drugs represent just a glimpse into the potential of oligonucleotides in medicine, with many more oligonucleotide-based therapies currently in clinical trials. The growing approval and success of these treatments have significantly increased the demand for high-quality oligonucleotide synthesis.

 

4. Market Demand for Oligonucleotides

The demand for oligonucleotides is expected to continue growing as research and development in gene therapy and personalised medicine accelerate. Several factors contribute to this increasing demand:

• Personalised Medicine: As the healthcare industry moves toward personalised treatments, the need for custom-designed oligonucleotides tailored to individual genetic profiles grows.
• Expanding Applications: Oligonucleotides are no longer confined to academic research. Their use in commercial drug development, gene therapy, and diagnostic tools is driving market growth.

 

5. The Importance of PMI in Oligonucleotide Manufacturing

Process Mass Intensity (PMI) is a key metric in oligonucleotide manufacturing, measuring the amount of raw materials required to produce a unit of product. This metric is critical for assessing and optimising the efficiency of the production process. Lower PMI values indicate more sustainable and cost-effective manufacturing practices, a goal of increasing importance in large-scale oligonucleotide synthesis.

By focusing on PMI, manufacturers can reduce material waste and enhance process efficiency while maintaining the high purity and consistency essential for therapeutic applications. Innovations like Exactmer’s Nanostar sieving and liquid-phase synthesis contribute significantly to achieving lower PMI, ensuring a balance between scalability and environmental responsibility.

 

Final Thoughts

Oligonucleotide synthesis is at the forefront of biotechnology, with applications that span diagnostics, gene therapy, and drug development. As the market for oligonucleotides continues to grow, manufacturers face both challenges and opportunities in meeting the increasing demand for these versatile molecules. Advances in synthesis technology, along with a focus on process optimisation, are paving the way for more efficient and cost-effective production.

At Exactmer, we understand the importance of high-quality oligonucleotide synthesis and are committed to delivering solutions that meet the demands of our clients and the broader biotech industry. To learn more about our services and how we can assist with your oligonucleotide synthesis needs, contact us today.

 

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Exactly defined molecular weight poly(ethylene glycol) allows for facile identification of PEGylation sites on proteins

We are thrilled to announce the publication of our new research paper titled “Exactly defined molecular weight poly(ethylene glycol) allows for facile identification of PEGylation sites on proteins” in Nature Communications!

Diagram illustrating the differences between conventional PEGylation and PEGylation defined in this publication. Using Exactmer's PEG synthesis for defined molecular weights enables for easy identification of PEGylated regions within a protein using relatively straightforward techniques.

Diagram illustrating the differences between conventional PEGylation and PEGylation defined in this publication. Using Exactmer’s defined molecular weight PEG synthesis enables for easy identification of PEGylated regions within a protein using relatively straightforward techniques.

In this study, we propose a chromatography-free synthesis process to produce defined PEGs with a molecular weight of 5kDa.

This breakthrough approach enables the use of precisely defined molecular weight poly(ethylene glycol) to address current batch-to-batch variations and unpredictable impurities in PEGylated drugs — an essential consideration for advancing biopharmaceutical development.

Our findings could transform how PEGylation, a key method to improve protein stability and therapeutic efficacy, is studied and applied in drug development.

We invite you to read the full paper and explore how Exactmer’s innovation could impact the future of drug design and protein synthesis. Find out more about how our findings on PEG synthesis can help you by visiting Our Services – Exactmer.

Read the full paper here:

Exactly defined molecular weight poly(ethylene glycol) allows for facile identification of PEGylation sites on proteins | Nature Communications