Oligonucleotide synthesis

Introduction to Oligonucleotide Synthesis Methods and Explanation of the Importance of Substrates

Oligonucleotides are short nucleic acid molecules composed of a few nucleotide units and are widely used in... Molecular diagnostics, targeted therapy, RNA interference, antiviral therapies, and gene editing and other fields. The currently mainstream synthesis technology is... Solid-phase phosphoramidite synthesis It features high synthesis efficiency, a high degree of automation, and precise sequence control.

Synthetic Core Steps and Key Substrates

Solid-phase synthesis of oligonucleotides generally involves the following cyclic steps:

Deprotection Remove the DMT protecting group from the 5' end;

Base coupling (Coupling) : Introduce a new phosphoramidite monomer to the chain terminus;

Oxidation/Sulfurization Stabilize the intermediate product;

Capping Terminate unreacted hydroxyl groups to prevent the extension of impurity chains.

The key substrates used include:

Nucleoside Phosphoramidites As the core raw material for extending each base, its structural accuracy and purity determine the synthesis efficiency and the quality of the final product.

Unylinker solid-phase carrier A support material that efficiently cleaves and leaves minimal residues, widely replacing traditional CPGs to improve yields and reduce impurity formation.

Protecting group nucleosides (e.g., DMT protection) : Ensure reaction directionality and sequence accuracy;

Reaction auxiliary reagent (Vulcanizing agents, oxidizers, end-group modifiers, etc.): Ensure chain integrity and reaction efficiency.

Downstream Modification—The Importance of GalNAc

In the field of nucleic acid drugs, GalNAc (trisaccharide of N-acetylgalactosamine) modification It is an important targeted delivery technology capable of achieving... Oligonucleotide molecules specifically enter hepatocytes. This significantly enhances in vivo bioavailability and therapeutic targeting. GalNAc is typically covalently attached to the terminal or side-chain structures of oligonucleotides and is widely used in siRNA and ASO drugs, such as Givosiran and Lumasiran, which have been approved by the FDA.

Oreva's solution

Aurife Bio-Technology Co., Ltd. has long been focused on High-quality oligonucleotide synthesis raw materials R&D and production, with a product portfolio covering:

High-purity natural and modified nucleoside monomers, Phosphoramidate compounds ；

Customized Unylinker solid-phase carrier , suitable for high-throughput synthesis platforms;

All kinds of GalNAc-modifying group and its intermediates , supporting the development of targeted nucleic acid drugs;

Key supporting reagents, including protected nucleoside building blocks, coupling agents, and amide-modifying reagents.

Oripharm deeply understands that **high-quality substrates are the essential foundation for producing premium oligonucleotides.** We are committed to providing customers with substrate solutions spanning the entire process—from research all the way to industrial-scale production—thereby accelerating the translation of nucleic acid technologies into clinical applications.

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