What are oligonucleotides?
Nucleotides are monomeric building blocks of nucleic acids like DNA and RNA. They each contain a nitrogenous base, a pentose sugar and a phosphate, and can be linked together to form a polymer chain.
Oligonucleotides, also referred to as oligos, are a short polymeric chain of 13–25 nucleotides. These oligonucleotides occur naturally but are typically synthesised for research and therapeutic applications. Due to their ability to bind to complementary nucleic acid bases, oligos are often used as primers for DNA amplification and as tools to treat diseases by modulating gene expression.
1 Nucleotide
1Phosphate
2Base
3Sugar
The same chain builds DNA and RNA
Oligonucleotide
13–25 nt
→
DNA / RNA
thousands–millions of nt
A short stretch of this same nucleotide chain, repeated many times over, makes up the full twisted double helix of DNA or RNA.
Types of Oligonucleotides
ASO
ASOs are short oligonucleotides. They target and are capable of altering mRNA expression in a precise way, such as by preventing the formation of disease-causing proteins, triggering the degradation of the mRNA, or modifying RNA splicing. Structurally, ASOs are typically single stranded, made up of 15–25 nucleotides.
siRNA
Small interfering RNA, known as siRNA, is a double stranded, non-coding short RNA molecule typically 20–25 base pairs long. It regulates gene expression through a process known as RNA interference (RNAi), using a gene silencing mechanism which is activated by degrading complementary mRNA.
miRNA
miRNA is a single stranded, non-coding short RNA molecule. It possesses a gene silencing mechanism by binding to target mRNA, causing translational repression to regulate gene expression.
saRNA
Small activating RNA, saRNA, is a double stranded, non-coding short RNA molecule. It regulates gene expression by binding to gene promoters, which stimulates transcription and increases gene expression. Unlike siRNA and ASOs, these oligos work by increasing rather than silencing genes.
The Bottleneck in Oligonucleotide Therapeutics Manufacturing
The success of oligonucleotide therapeutics has been largely attributed to their ability to treat rare diseases, particularly those caused by genetic mutations. In recent years, the pharmaceutical applications of oligonucleotides have expanded to show great potential in treating prevalent diseases. Now, several oligonucleotide-based drugs targeting diseases with large patient populations — such as cardiovascular disease, Alzheimer’s and Hepatitis B — are progressing through the clinical trial pipeline, on their way to revolutionising treatments for affected patients.
However, once approved, these drugs are at risk of being inaccessible to patients due to high costs and limited manufacturing capacity.
Existing manufacturing techniques such as solid phase oligonucleotide synthesis work efficiently at smaller scales, perfect for manufacturing rare disease therapeutics. As advances in medicine mean increasing genetic targets are found for prevalent diseases, the industry now requires novel, scalable and efficient manufacturing solutions to ensure the commercial viability and accessibility of these upcoming blockbuster drugs.
Nanostar Sieving™: A Precise and Scalable Synthesis Method for Oligonucleotides
Nanostar Sieving™ features an automated, fully liquid phase process which reduces solvent consumption, creating a cost-effective manufacturing process for oligonucleotide therapeutics. The process holds the record for the longest oligo to be made exclusively in the liquid phase (21-mer), and is excelling in the production of oligo fragments (15-mer). Learn more about our technology.
The Advantage of the Nanostar Sieving™ Platform for Oligonucleotide Synthesis
Cost-effective manufacturing
Nanostar Sieving™ has significantly decreased manufacturing costs through an enhanced process characterized by reduced solvent consumption, minimized reagent equivalents, less expensive soluble supports and real-time monitoring of reaction completion.
Unprecedented scalability
Our liquid phase process is highly scalable which will help improve manufacturing efficiency and meet the demand for therapeutics treating prevalent diseases.
Chemistry agnostic platform
This chemistry agnostic platform allows us to use and explore various chemistries and process improvements (e.g P(III), P(V), fragments).
Highly flexible and compatible
The Nanostar Sieving™ platform can be integrated into existing manufacturing assets (solid phase train and small molecule).
Reduced environmental impact
Our process uses a single solvent mixture, allowing the recycling of the used solvent and reducing the total Process Mass Intensity (PMI).
Explore the use of the Nanostar Sieving™ platform
Process development
Process Scale up
Technology transfer
Membrane Supply & Licensing
Supply of polymers
Strategic partnership
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