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Random Copolymers Enabling Nonimmunogenic PEGylation for Medical Therapeutics

Project description

Overcoming the immunogenicity of polyethylene glycol-conjugated drugs

Polyethylene glycol (PEG) is a biocompatible polymer used in the medical industry as a bioconjugate to improve the pharmacokinetic properties of drugs. Conjugation of drugs with PEG prolongs their systemic circulation and renders them non-immunogenic. However, emerging evidence indicates that certain patients develop anti-PEG antibodies, leading to hypersensitivity and drug clearance. Funded by the European Research Council, the RandoPEGMed project aims to address this problem by modifying PEG polymers to eliminate immune recognition. Given the importance of PEG for drug delivery, researchers hope to maintain its pharmaceutical use and increase its safety.

Objective

PEGylation, the attachment of the highly hydrophilic, biocompatible polymer polyethylene glycol (PEG) to therapeutics, has become a key strategy in current nanomedicine. PEGylation is indispensable for a broad variety of commercial therapeutics. They range from protein drugs to relevant nanocarriers, such as liposomes and lipid nanoparticles. PEG leads to the particular stealth effect, i.e. strongly prolonged blood circulation times and apparent invisibility for the immune system. This is also used for lipid nanoparticles (LNP) transporting mRNA vaccines, used worldwide against the COVID-19 pandemic. However, this powerful weapon is now in danger of becoming blunt: An increasing body of literature from immunologists, clinicians and biochemists shows a rapid increase of individuals (50-70% in industrialized countries) possessing anti-PEG antibodies (APAs). This causes undesirable rapid elimination of PEGylated drugs from the bloodstream, hypersensitivity and strong allergic reactions. RandoPEGMed introduces PEG-derived random copolymers for nanomedicine. These PEG copolymers with well-defined chain length possess randomly distributed point mutations along the chains, which both disables recognition by the immune system and formation of antibodies. The project will thus exploit monomer sequence statistics to eliminate immunogenicity, representing a radically new approach in polymer therapeutics. One pivotal aim is precise understanding of monomer sequence statistics in the anionic copolymerization of glycidyl ether monomers with ethylene oxide (EO). At the interface of polymer synthesis, pharmaceutical chemistry and medicine this project aims at preserving the benefits of PEGylation for the future. Based on our preliminary results and the hypothesis that anti-PEG antibodies cannot be formed against random PEG copolymers, this concept will have vast therapeutic implications for polymer conjugates, therapeutic nanoparticles and stealth liposomes.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2021-ADG

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Host institution

JOHANNES GUTENBERG-UNIVERSITAT MAINZ
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 477 433,00
Address
SAARSTRASSE 21
55122 MAINZ
Germany

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Region
Rheinland-Pfalz Rheinhessen-Pfalz Mainz, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 499 933,00

Beneficiaries (2)

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