PEGylation technology: addressing concerns, moving forward.

Abstract

PEGylation technology, that is grafting of poly(ethylene glycol)(PEG) to biologics, vaccines and nanopharmaceuticals, has become a cornerstone of modern medicines with over thirty products used in the clinic. PEGylation of therapeutic proteins, nucleic acids and nanopharmaceuticals improves their stability, pharmacokinetic and biodistribution. While PEGylated medicines are safe in the majority of patients, there are growing concerns about the emergence of anti-PEG antibodies and their impact on the therapeutic efficacy of PEGylated medicines as well as broader immune responses, particularly in complement activation and hypersensitivity reactions. These concerns are beginning to scrutinize the future viability of PEGylation technology in medicine design. Here, we outline these concerns, encourage more efforts into looking for comprehensive scientific evidence on the role of anti-PEG antibodies in hypersensitivity reactions, discuss alternatives to PEG and propose strategies for moving PEGylation technology forward.