Vital Funding supports Investigation of PEG Variants

To prevent active biopharmaceuticals from being attacked by our immune systems a standard procedure used since the 1980’s has been to create a "cloak of invisibility" around the drug by means of conjugation with the polymer polyethylene glycol (PEG). The mRNA vaccines designed to protect against infection with the coronavirus are, for example, PEGylated. More recently however, problems associated with this concept have been emerging; this includes studies revealing a rise in the number of individuals who are developing antibodies against PEG, which potentially could trigger severe allergic reactions.

Professor Holger Frey of Johannes Gutenberg University Mainz (JGU), who has been awarded an ERC Advanced Grant worth EUR 2.5 million to support his research, is in the process of developing a novel procedure intended to sidestep the drawbacks of PEGylation, but at the same time preserve its benefits.

"PEGylation of many commercially available drugs is absolutely indispensable," emphasised Professor Frey. "Without this, our bodies would identify the related active substances, including mRNA vaccines, as dangerous intruders and would rapidly degrade and excrete them. The camouflage effect has worked well for the past 30 years, but it looks like the magic is wearing off."

The purpose of the ERC-sponsored project RandoPEGMed, is thus to create modified polymers for conjugation with medicinal agents, the basis of which would still be polyethylene glycol, but which in the form of a PEG which has been supplemented with additional building blocks.

"What we are planning to do is break down the uniform structure by the insertion of randomly distributed irregularities," Frey clarified. "This should restore the masking effect, enabling the drugs to reach their intended destinations without being discovered by the immune system."

Using the experience gained with his research team during the last decade Holger Frey, Professor of Organic and Macromolecular Chemistry at JGU and an internationally recognised expert in the field of polyether chemistry, has come up with a method for analysis of polymer structures on the molecular level.

The Advanced Grant is the EU's most richly endowed funding program, awarded by the European Research Council (ERC) to outstanding researchers.

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