PEGylation of Oligonucleotides

BOC Sciences provides high-quality PEGylation services of oligonucleotides. We can add high-performance activated PEG with different molecular weights, terminal functional groups, and different degrees of branching at multiple positions in the oligonucleotide. By using this service, customers can obtain therapeutic oligonucleotides with superior properties in the fields of cellular uptake, gene regulation efficacy, side effect reduction, and biodistribution. We are also able to meet your PEGylation needs from laboratory scale through large commercial scale.

What Are Oligonucleotides?

PEGylation of Oligonucleotides

Oligonucleotides (ONs) are short DNA or RNA sequences that are considered a new class of "message" therapeutics. Because of their unique mechanism of regulating disease gene transcription at the RNA level, oligonucleotide drugs are expected to be used in multiple therapeutic fields for rare diseases and refractory diseases. However, unmodified, naked ONs are easily degraded by nucleases, can undergo rapid renal and hepatic clearance, and are hopelessly incapable of cellular entry owing to a combination of hydrophilicity and high molecular weight (MW). These factors greatly limit the research and application of oligonucleotide drugs.

Benefits of PEGylation of Oligonucleotides

PEGylation has been widely recognized as one of the more promising approaches for exploring the use of therapeutic drugs and improving the therapeutic efficacy of drugs in clinical settings. PEGylation increases nuclease resistance and the circulating half-life of oligonucleotides. Therefore, the stabilization of oligonucleotides with PEG is a promising approach for the development of therapeutic oligonucleotides.

Oligonucleotides PEGylation Capabilities

Our custom PEGylation services include but are not limited to:

  • Synthesis of custom activated PEGs
  • Feasibility study of PEG-oligonucleotide conjugates
  • Establishment of the PEGylation process
  • Optimization of PEGylation and purification process
  • Pilot production of PEG-oligonucleotide conjugates
  • Analytical method development and pre-validation
  • In Vitro and animal studies

Oligonucleotides PEGylation Processes and Techniques

We successfully generated a large library of PEGylated ONs with different PEG MW and conjugation sites, including a series of brush, star, and micellar ON conjugates. We are proficient in various synthesis techniques:

  • High-efficiency liquid phase (HELP) synthesis
  • Organic solvent nanofiltration (OSN)
  • Conjugation chemistry (including Michael addition, disulfide exchange, amidation reaction, and copper-catalyzed and copper-free click chemistries)
  • Enzymatic ligation (e.g., with T4 DNA ligase)

This modular approach allows the creation of large quantities of PEG conjugates without the need for PEG-ON conjugation and purification each time, reducing synthetic costs.

Chemical synthesis of PEGylated ONs.Fig. 1. Chemical synthesis of PEGylated ONs.[1]

Oligonucleotides PEGylation Purification

Liquid couplingUse pre-purified ON to ensure that all conjugates have the correct ON sequence. PEGylated ON was successfully purified from unreacted ON and PEG by reversed-phase high-performance liquid chromatography (RP-HPLC), gel electrophoresis, and ion-exchange chromatography, resulting in prolonged elution times.
Solid phase couplingPurification is simplified by ensuring that there is no unreacted PEG, yielding conjugates with the correct ON sequence.

As a global supplier, BOC Sciences' custom PEGylation services of oligonucleotides always follow a strict quality control process, including the delivery of COA, MS, HPLC and/or other analytical data of the final product. Based on the advanced PEGylation platform, we also provide complete PEGylation method development services to fully support customers' oligonucleotide therapy research.

Contact us online with your detailed project specifications and we will help you design and develop the most suitable synthesis method for you.


  1. Lu X, Zhang K. PEGylation of therapeutic oligonucleotides: From linear to highly branched PEG architectures. Nano Res. 2018, 11(10): 5519-5534.

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BOC Sciences supplies a unique variety of PEG derivatives and functional PEG polymers. Our products offer the most diverse collection of reactivity, ready-to-use functionality, and molecular weight options that you will not find anywhere else.

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