FARO Academy

PEGylation can provide additional water solubility and immunogenicity improvements to nucleic acid fragments or oligonucleotides, allowing nucleic acid drugs to be delivered to target regions at more effective doses.

Oligonucleotides PEGylation

Polyethylene glycol is one of the most commonly used biomolecular modification and binding reagents, with excellent biocompatibility and operability. PEG is usually prepared from ethylene oxide through an anionic ring-opening reaction, which can yield linear or branched PEG polymers with molecular weights ranging from 2.5 kDa to over 50 kDa. The use of PEG polymers in bioconjugation applications can significantly improve the water solubility and immunogenicity of the modified molecules, protect the modified molecules from enzymatic digestion and cleavage, and effectively increase the molecular bulk to avoid renal filtration. These characteristics can significantly improve the pharmacodynamics and pharmacokinetic parameters of nucleic acid/oligonucleotide drugs.

Methods of Oligonucleotides PEGylation

There are several possible ways for PEG molecules to be conjugated to nucleic acids/oligonucleotides depending on the chosen process. PEG can be modified by NHS to form NHS-PEG bifunctional or heterobifunctional crosslinkers, which can react with thiol-modified RNAs and crosslink with thiols. PEG-polycationic diblock copolymers added with specific diamine side chains can encapsulate siRNA into complex micelles with high escape ability in vivo. Lactosylated PEGs can be conjugated to oligonucleotides via acid-labile β-thiopropionate linkages to create pH-sensitive copolymers. PEG can also be used directly as an encapsulating material or combined with liposomes to form organic hybrid nanoparticles to provide better structural stability and drug aggregation ability. In addition, PEG can modify cyclodextrin-starburst polyamidoamine (PAMAM) dendrimer polymers and form polypseudorotaxanes, which can be used for sustained release of gene or oligonucleotide drugs.