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Controlled Degradable Polymer Carriers for mRNA Vaccination: From Pathogens to Personalized Cancer Immunotherapy

Project description

Next generation nanocarriers for mRNA vaccines

mRNA vaccines introduce synthetic RNA into cells via lipid nanoparticles. This mRNA produces specific proteins that activate protective immune responses. During the COVID-19 pandemic, the mRNA technology saved millions of lives by enabling rapid vaccine development and production. However, existing lipid nanoparticle carriers present issues with stability, require cold storage and they exhibit a risk for immune-related side effects. The ERC-funded PolymeRNA project aims to address these issues by developing polymer-based, lipid-free nanocarriers. These novel carriers offer enhanced stability and precise delivery control. In addition, they can facilitate targeted RNA release while it is also possible to co-deliver immune modulators, opening new avenues for next-generation vaccines.

Objective

The tragic outbreak of the COVID-19 pandemic stimulated research to go beyond common grounds and develop powerful vaccines against the SARS-CoV-2 virus. A new vaccine technology based on messenger RNA (mRNA) was translated into almost one billion patients and saved millions of lives. It addresses the needs of rapid, scalable and adaptable vaccine production. However, mRNAs require potent nanocarriers to prevent the RNA strands from extracellular degradation and enable their uptake into antigen-presenting cells. During urgent development, established lipid-based nanoparticles (LNPs) were used for mRNA encapsulation, yet, they provided limited long-term stability and required strict temperature storages, which prevented their distribution to locations with no cold storage options. Moreover, several patients experienced hard-to-control immunological adverse effects that were associated with some of the lipid components.
In my ERC proposal, I therefore want to pioneer a novel and unprecedented macromolecular approach that will overcome these issues and introduce polymer-based and lipid-free, lyophilizable nanocarriers for intelligent mRNA delivery. I will generate self-immolative poly(carbonate)s with reductive decationizable features for controlled RNA complexation, as well as stimuli-responsive release and carrier depolymerization upon entry into antigen-presenting cells. Co-delivery of small molecule immune modulators will enable precise control over quality and quantity of the pursued humoral and cellular immune responses. Moreover, reversible core-crosslinking and surface conjugation with relevant targeting units will foster systemic in vivo applications towards immunization against infectious diseases and cancer.
Elaborating multi-responsive macromolecular tools on an mRNA-binding polymer will become a groundbreaking asset for mRNA delivery, circumvent today’s still not overcome hurdles and enhance its access to and acceptance by the general public.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2024-COG

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Host institution

JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Net EU contribution
€ 1 999 998,75
Address
SANDERRING 2
97070 Wuerzburg
Germany
Region
Bayern Unterfranken Würzburg, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 2 000 000,00

Beneficiaries (1)