PEG: Will It Come Back to You? Polyethelyne Glycol Immunogenicity, COVID Vaccines, and the Case for New PEG Derivatives and Alternatives

• Type of Material: Article
• Authors: Yi Wen Kong, Massachusetts Institute of Technology; Erik Dreaden, Emory University
• Language: English
• Date: 2022-04-27
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Kong and Dreaden.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fbioe.2022.879988
• Title of Journal or Parent Work: FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
• Volume: 10
• Start Page: 879988
• End Page: 879988
• Grant/Funding Information: This work was supported in part by the American Association of Cancer Research UK, the Coulter Department of Biomedical Engineering, and the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta.
• Keywords: SULFUR-HEXAFLUORIDE SONOVUE; polymer chemistry; Science & Technology; nanotechnology; POLYETHYLENE-GLYCOL; drug delivery; INNATE IMMUNE-RESPONSE; Biotechnology & Applied Microbiology; REPEATED INJECTION; COMPLEMENT ACTIVATION; nanomaterials; ACUTE LYMPHOBLASTIC-LEUKEMIA; POLY(ETHYLENE GLYCOL); PEG; Multidisciplinary Sciences; ACCELERATED BLOOD CLEARANCE; Life Sciences & Biomedicine; PEGYLATED LIPOSOMES; Science & Technology - Other Topics; ACTIVATION-RELATED PSEUDOALLERGY
• Research Categories: Health Sciences, Oncology

Abstract

Polymer-drug conjugation (Harris, 1992; Harris and Chess, 2003; Haag and Kratz, 2006; Pelegri-O’Day et al., 2014; Hoffman, 2016; Ekladious et al., 2019) was first described in the 1954 by German chemist, Horst Jatzkewitz, who demonstrated that covalent attachment of poly (vinyl pyrrolidone) to the psychoactive compound, mescaline, could be used to prolong its circulation and duration of action (Figure 1A) (Jatzkewitz, 1954; Jatzkewitz, 1955; Luxenhofer, 2020). Yet despite its novelty and utility, Jatzkewitz’s innovation went largely unnoticed until the mid 1970s when it was revived by Ringsdorf, Kopecek, and Duncan, among others, who championed the notion that these novel macromolecules could enhance the suboptimal activity of various pharmaceuticals (Ringsdorf, 1975). It wouldn’t be until 1990—nearly 36 years from the publication of Jatzkewitz’s initial work—that the first polymer-drug conjugate would receive market approval in the form of Adagen, adenosine deaminase protein conjugated with 5 kDa poly (ethylene glycol), or PEG, used to treat a rare and hereditary, pediatric metabolic disorder called adenosine deaminase severe combined immunodeficiency (Hershfield et al., 1987).