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.