Federica Sebastiani

Project title

Decoding the Biological Identity of mRNA Lipid Nanoparticles for Next-Generation Vaccines

What is your project about?

This project aims to improve messenger RNA (mRNA) vaccines, such as those used against COVID-19. Vaccination is one of the most effective public health interventions, and mRNA vaccines represent a major breakthrough enabled by advances in biotechnology. These vaccines rely on lipid nanoparticles (LNPs) to protect and deliver mRNA into cells. Once in the body, these particles interact with biological molecules and quickly acquire a coating of proteins, known as a “protein corona”.    

The project investigates how this protein corona influences where nanoparticles travel in the body and how efficiently they deliver their cargo. By understanding these interactions in more detail, the goal is to support the design of more effective and predictable delivery systems. In the long term, this could contribute to more efficient and adaptable mRNA-based vaccines and therapies.

How did you become interested in your particular field of research?

I have been interested in mathematics and physics from an early stage, particularly in the challenges they offer. After a Bachelor’s degree in Physics, I became increasingly fascinated by biophysics and by how physical approaches can help understand biological systems. During my Master’s thesis, I spent time at the Institut Laue-Langevin in Grenoble, where I worked on lipids and their self-assembly. This experience made me realize that I wanted to work at the interface between physics and biology, with a particular focus on drug delivery.      

In 2019, I was awarded a postdoctoral grant to study interactions between serum proteins and lipid nanoparticles for mRNA delivery. This marked a shift toward applying physical methods to fundamental questions in drug delivery systems.

What are the scientific challenges and perspectives in your project?

A key scientific challenge is the limited understanding of how lipid nanoparticles behave in the complex biological environment encountered after administration. While it is known that they rapidly acquire a coating of biological molecules, the rules governing how this evolves and how it influences biological outcomes remain poorly understood. This uncertainty makes it difficult to fully predict and control the performance of mRNA delivery systems.    

The project aims to contribute to a more fundamental understanding that can support better design principles for future lipid nanoparticles. In the long term, this could help move the field away from trial-and-error approaches and towards more rational development of mRNA medicines, improving both vaccines and therapeutic applications.

What is your estimate of the impact, which your project may have to society in the long term?

This project aims to improve the ability to predict and influence how lipid nanoparticles interact with biological environments, with the goal of enhancing uptake in target cells and increasing the efficiency of mRNA delivery. This could enable higher therapeutic efficacy at lower doses, reducing side effects and lowering production costs.    

A key outcome is the development of a new platform to study nanomedicine in biomimetic, muscle-like matrices, providing more realistic conditions that better reflect biological complexity. By integrating this complexity early in formulation design, the platform aims to bridge in vitro and in vivo outcomes and support more rational drug delivery strategies.    

In the long term, this may reduce the gap between preclinical and clinical studies and decrease reliance on animal testing by improving early predictive capability.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

The project supported by the Saper Aude programme will be an important stepping stone in my academic career and in my ambition to become an independent research group leader. It will allow me to further develop my leadership skills through both formal training and hands-on mentoring experience. At the same time, I will strengthen my national and international collaborations and work toward expanding my research activities by pursuing additional funding opportunities.  

Scientifically, I aim to position my future research at the interface of biophysics, biology, and drug delivery, with a focus on advancing scattering-based techniques that capture biological complexity. These approaches can provide deeper structural and mechanistic insight into vaccine formulations and their modes of action, helping to bridge fundamental science and translational applications.