New invisibility cloak for therapeutics: Holger Frey receives ERC Advanced Grant to support his innovative research
Future process aims at preserving the advantages of PEGylation for the use in nanomedicine while avoiding recognition of the new PEG structures by the immune system
26 April 2022
Since the first PEGylated drug was developed in the 1980s, the so-called PEGylation has become a standard procedure in the pharmaceutical sciences. The technique involves concealing active biopharmaceuticals under a kind of "cloak of invisibility" by means of conjugation with the polymer polyethylene glycol (PEG). Consequently, they are not subjected to rapid degradation or undesirable attack by the immune system. The mRNA vaccines designed to protect against infection with the coronavirus are, for example, PEGylated. Unfortunately, problems with the concept are emerging, since an increasing number of individuals is developing antibodies against PEG, which in some instances can trigger severe allergic reactions. Professor Holger Frey of Johannes Gutenberg University Mainz (JGU) is currently developing a novel procedure intended to sidestep the drawbacks of PEGylation, but at the same time preserving its benefits. He has been awarded an ERC Advanced Grant worth EUR 2.5 million to support his research. An Advanced Grant is the EU's most richly endowed funding program, awarded by the European Research Council (ERC) to outstanding researchers. Holger Frey has been Professor of Organic and Macromolecular Chemistry at JGU since 2002 and is an internationally recognized expert in the field of polyether chemistry.
PEGylation – a key strategy of current nanomedicine
Polyethylene glycol is a substance that is fairly ubiquitous. It is present in cosmetics, toothpaste, detergents, lithium-ion rechargeable batteries, foodstuffs, and textiles. PEG is employed in pharmaceutical technology and medicine as a carrier medium for active substances and in an extensive range of special applications. On the molecular level, PEG really comes into its own when it is conjugated with biopharmaceuticals and proteins to protect these through the process known as PEGylation. "PEGylation of many commercially available drugs is absolutely indispensable," emphasized Professor Holger 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."
This is due to our immune system, which in many individuals no longer allows the polymer to circulate undetected in the bloodstream. The results of recent studies indicate that up 70 percent of the population in developed countries has antibodies against PEG; in the early 1980s, the corresponding percentage was just one to two percent. The result is that the immune system often quickly removes drugs conjugated with PEG from the blood circulation so that they are unable to develop their therapeutic effects. Moreover, there can also be intolerance and even severe allergic reactions – effects that the technique was originally meant to prevent.
Research group to develop special PEG structures for use with medical drugs
One solution to this problem would be to devise new PEG-derived structures for use in medicine that differ from those exploited in everyday products. The purpose of the ERC-sponsored project RandoPEGMed is thus to create modified polymers for conjugation with medicinal agents. The basis will still be polyethylene glycol, but a PEG supplemented by 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." Professor Holger Frey has many years of experience in this particular area. Over the past ten years and with the help of his team of 25 personnel, he has come up with a method that allows to precisely analyze polymer structures on the molecular level.
ERC Advanced Grants: Recognition for international top-level research
Holger Frey studied chemistry at the University of Freiburg and, following study periods in the USA and France, obtained his doctorate at the University of Twente in the Netherlands. He has been Professor of Organic and Macromolecular Chemistry at JGU since 2002. His research field is new polymer materials including polymers for medical and pharmaceutical use as well as bio-based, potentially sustainable materials that could be used as alternatives to plastics made from fossil raw materials. The results of his research have appeared in more than 400 original publications and review articles while he has also obtained more than 40 patents. In addition, he is an associate editor of Polymer Chemistry of the Royal Society of Chemistry, one of the leading journals in the field of polymers. Among the various undertakings he is involved in at JGU, he is also co-project coordinator of Collaborative Research Center 1066 that targets nanodimensional polymer therapeutics for tumor therapy. This is an interdisciplinary research network that involves significant collaboration between the fields of chemistry, the pharmaceutical sciences, and medicine.
ERC Advanced Grants are awarded to outstanding researchers to enable them to work on projects considered to be highly speculative due to their innovative approach, but which, because of this, can open up access to new approaches in the corresponding research field. Only researchers who have already made significant breakthroughs and have been successfully working for at least ten years at the highest levels of international research are eligible for the grant. The only criteria considered in awarding ERC funding are the academic excellence of the researcher in question and the nature of their research project. An ERC grant thus also represents an important acknowledgement of the recipient's individual achievements.