Oligonucleotide Synthesis
Nanostar Sieving® has demonstrated success on one of the toughest challenges in upstream oligonucleotide synthesis.
One of several applications built on our OSN membrane platform.Nanostar Sieving® — the next generation of polymer synthesis in liquid phase
Where liquid phase polymer synthesis and our advanced membranes meet, to enable superior manufacturing of advanced therapeutics.
The Nanostar Sieving® platform is built on Organic Solvent Nanofiltration separation, using our proprietary Exact-10™ membranes. It allows synthesis of exact polymer pharmaceuticals fully in liquid phase, using a single solvent mixture, without precipitation or extraction steps.
A first monomer is attached to a central hub molecule, creating a "nanostar" with enhanced molecular size.
Further monomers are added iteratively, with the growing polymer purified at every step via purpose-designed nanomembrane filtration.
Separation happens purely by molecular size, so the platform is chemistry-agnostic and slots into our semi-automated Nanostar Synthesiser.
The Advantage of the Nanostar Sievingâ„¢ Platform for Oligonucleotide Synthesis
Cost-effective manufacturing
Reduced solvent, lower amidite equivalents
Unprecedented scalability
Highly scalable liquid phase process
Chemistry agnostic platform
Various chemistries — P(III), P(V), fragments
Highly flexible and compatible
Integrates into existing manufacturing assets
Reduced environmental impact
Solvent recycling, fewer acids, greener reagents
Ergonomic and efficient
No heavy resin columns, less manual handling
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.
2Base
3Sugar
How an oligonucleotide drug works
Many oligonucleotide therapeutics work by binding directly to the messenger RNA (mRNA) that would otherwise be translated into a disease-causing protein, stopping the harmful protein from ever being expressed.
Disease-causing mRNA
A faulty or overactive gene produces mRNA that codes for a harmful protein.
Oligo binds by base pairing
The therapeutic oligo matches and binds the target mRNA sequence exactly.
Protein is never made
Bound mRNA is degraded or blocked from translation, silencing the gene.
Shared mechanism for ASOs, siRNA and miRNA. saRNA works in reverse — increasing rather than silencing expression.
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, their pharmaceutical applications have expanded to show potential in treating prevalent diseases. Several oligonucleotide-based drugs targeting diseases with large patient populations, such as cardiovascular diseases, Alzheimer’s and Hepatitis B, are now progressing through clinical trials, 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 techniques such as solid phase oligonucleotide synthesis work efficiently at smaller scales, making them ideal for rare disease therapeutics. As more genetic targets are identified for prevalent diseases, the industry requires novel, scalable and efficient manufacturing solutions to ensure the viability and accessibility of these upcoming blockbuster drugs.
01
Manufacturing Cost
Existing solid phase methods carry high reagent and solvent costs, which don’t scale down favourably for large-scale manufacturing.
02
Capacity Constraints
Solid phase infrastructure is optimised for small-batch, rare-disease production — not the tonnes-per-year scale prevalent diseases require.
03
Expanding Patient Populations
As more prevalent-disease targets reach late-stage trials, the industry needs a synthesis platform built for scale from the outset.
Types of Oligonucleotides
Single-stranded · 15–25 nt
ASO
Alters mRNA expression, preventing disease-causing proteins, degrading mRNA, or modifying splicing.
Read more
ASOs target and alter mRNA expression precisely, by preventing disease-causing proteins, degrading mRNA, or modifying RNA splicing.
Double-stranded · 20–25 bp
siRNA
Silences genes through RNA interference (RNAi), degrading complementary mRNA.
Read more
siRNA is a double stranded, non-coding short RNA molecule, typically 20–25 base pairs, regulating gene expression through RNAi.
Single-stranded
miRNA
Represses translation by binding target mRNA, regulating gene expression.
Read more
miRNA is a single stranded, non-coding short RNA molecule with a gene silencing mechanism via translational repression.
Double-stranded · the exception
saRNA
Increases rather than silences gene expression, by binding gene promoters.
Read more
saRNA is double stranded and non-coding, regulating gene expression by binding promoters to stimulate transcription — increasing rather than silencing genes.
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