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PEGylation defines the modification of a protein, peptide or non-peptide molecule by the linking of one or more polyethylene glycol (PEG) chains. This polymer is non-toxic, non-immunogenic, non-antigenic, highly soluble in water and FDA approved.

The history of chemical modification of proteins has been long. Since the study of protein structure, biochemists have used various chemical methods to modify the amino acid side chain groups of proteins such as sulfhydryl, amino, imidazolyl, sulfhydryl and fluorenyl groups, linking various chemical groups to examine protein structure and functional changes. Therefore, when Professor Davis's research on PEGylated proteins was published, it did not cause many repercussions in the biochemistry community.
Moreover, when the enzyme is modified, the measured catalytic activity is reduced. From this point on, some people have a negative attitude towards PEGylation. Although modification can reduce the immunogenicity of proteins, the dramatic decline in biological activity has led researchers to give up on further exploration. However, when people enter the modified protein into the animal and measure its biological activity, it is found that the biological activity in the body is unexpectedly high and lasts for a long time.
This discovery has inspired biotech companies because they can use this technology to develop long-lasting genetically engineered protein drugs. It has low activity in vitro and high activity in vivo, and it is a common phenomenon of PEGylated proteins, which many people have not thought of before.
 
Further studies have found that the increase in vivo activity is related to the molecular weight of PEG: An increase in molecular weight usually increases the drug's half-life in the body, thereby facilitating the production of higher molecular weight mPEG, 10,000 to 20,000, 30,000 or even 40,000, by polyethylene glycol manufacturers. Branched PEG was also synthesized and exhibited a better prolongation of half-life in vivo than linear PEG of the same molecular weight.
So far, the listed PEGylated protein drugs have increased several times more than the half-life of the original drug. The use of the drug change from the original one needle per day to one needle per week which greatly facilitates the patient and also improves the drug efficiency. For example, PEGylated interferon is superior to unmodified interferon in the treatment of hepatitis C. Therefore, the original intention of PEGylation change from overcoming the immunogenicity to prolonging the efficacy and improving the therapeutic effect.