Antisense oligonucleotides (ASOs) regulate the expression of specific genes by inhibiting the translation or promoting the degradation of mRNAs through complementary pairing with target mRNAs, which is widely used in gene function studies, targeted therapy and gene silencing.

The global oligonucleotide drugs market is exhibiting strong growth momentum, with the current market size growing from USD 0.01 billion in 2016 to USD 3.25 billion by 2021, at a CAGR of 217.8%. The global oligonucleotides market size is expected to reach USD 15 billion by 2026.

North America is the largest region in the global oligonucleotide synthesis market, followed by Europe and Asia Pacific. The growth in these regions is driven by the increase in research activities in the pharmaceutical and biotechnology industries and growing demand for advanced therapeutic and diagnostic procedures.

The oligonucleotide synthesis market is characterized by diverse manufacturers, product types, and applications catering to the needs and preferences of different users. The prevalence of infectious diseases such as COVID-19 has led to an increase in the demand for oligonucleotide therapeutics; increased R&D investments by pharmaceutical and biotechnology companies to create oligonucleotide solutions with higher therapeutic potential and fewer adverse effects; government support for synthetic biology and genome projects; and an increased focus on customized drugs.

Market trends such as technological advancements, sustainability, customization, and digital transformation are shaping the growth and development of the oligonucleotide synthesis market.

Marketed ASOs Drugs

ASOs Pharmacokinetic Profile

ASOs are generally more bioavailable when administered subcutaneously, and localized therapy can also be achieved from local injections such as intravitreal or intrathecal, which can be widely distributed in the central nervous system (spinal cord and brain) after intrathecal administration, e.g., Nusinersen, which is used for the treatment of spinal muscular atrophy, is injected directly intrathecally.

Whether administered intravenously or subcutaneously, plasma concentrations decline rapidly from Cmax in a polyphasic manner and are rapidly distributed from plasma to tissues within minutes to hours, followed by one or slower disposition phases up to a terminal elimination half-life of 4 weeks to 2 months. The longer terminal elimination half-life in plasma represents tissue redistribution to the plasma compartment and reflects the slow transfer of tissue cells to the extracellular fluid and plasma compartments.

During the tissue-to-plasma redistribution phase, plasma and liver drug concentrations are generally in a relatively fixed ratio, e.g., the plasma:liver concentration ratio of 2ʹ-MOE ASOs is approximately 1:5000, a ratio that remains consistent across species, suggesting that the plasma drug concentration detected can be used to extrapolate drug concentrations accumulating at the liver site.

ASOs circulate throughout the body in the bloodstream, distributing more than 80% of the drug in the liver and kidneys, and are metabolized predominantly by nucleic acid exonucleases and endonucleases in the bloodstream and tissues; therefore, the half-life of ASOs correlates with the metabolic stability of the 2ʹ chemical modification. Prototype and nuclease metabolites are excreted primarily via urine.

With the exception of morpholino-ASOs, other ASOs contain PS backbones that allow extensive binding to albumin, with plasma protein binding greater than 85%, and the high protein binding is effective in reducing glomerular filtration and urinary excretion.

Eteplirsen, a morpholino-substituted ASO approved for marketing, has a protein binding ratio of 6.1% to 16.5% and a renal excretion clearance of 60% to 70% within 24 h despite good metabolic stability with chemical modifications.

Synbio Technologies | ASOs Synthesis

Synbio Technologies produces high quality ASOs that have maximum binding affinity and stability. Our antisense oligos are ableto recognize specific mRNA sequences, thus blocking the translation of corresponding proteins, ultimately leading to the inhibition of gene expression.

ASOs Design：We can design three ASOs according to the target gene sequences provided by customers, and ensure that at least one of them can effectively inhibit the expression of the corresponding gene, i.e., the inhibition efficiency at the mRNA level is above 70%.

ASOs Synthesis：After performing ASOs design, we synthesize customized oligonucleotides using state-of-the-art methods and cutting-edge technologies such as high-performance liquid chromatography purification and electrospray mass spectrometry (ESI-MS) to ensure the highest purity and accuracy.

Antisense oligonucleotides synthesis