VECT-PI

Lipid nanoparticles (LNPs) enabled the launch of mRNA as a medicine in 2020 in the context of the COVID-19 pandemic. This spectacular breakthrough should not obscure the fact that less than 5% of the mRNA is delivered into cells, which means that mRNA and LNPs must be administered in higher doses, potentially causing unwanted side effects. Furthermore, current commercial lipids are only available at exorbitant prices.
The VECT-PI project aims to design new lipids to deliver mRNA more effectively. The challenges are to obtain lipids that are well tolerated by the body and that can be produced at low cost. The expected impacts are a broadening of potential medical applications and greater sovereignty for France.
The work is divided into six main areas:
1. Design and develop innovative lipids to optimise mRNA complexation and release
2. Create a series of formulations produced by microfluidics, supported by a computational and automated approach.
3. Develop new physicochemical methods to generate quantitative data on LNP/mRNA binding and dissociation
4. Effectively measure endosomal release in vitro using advanced spectroscopic techniques.
5. Determine the biodistribution and pro-inflammatory or tolerogenic profile of the formulations to guide their subsequent therapeutic applications.
6. Evaluate the lipids in relevant diseases (cancer/psoriasis) in light of their Th1/Th2 profile determined in step 5.

COVID-19 vaccines have demonstrated the potential of messenger RNA, or mRNA, as a new tool for preventing and treating certain diseases. To deliver mRNA into cells, researchers use lipid nanoparticles, which are tiny structures made of lipids that surround and protect the mRNA.

However, current delivery systems still have several limitations. A large proportion of the mRNA can remain trapped inside cells without being able to perform its intended function, while the amounts required can sometimes cause unwanted side effects. In addition, some components of these nanoparticles can trigger an inflammatory response, and the lipids needed to produce them can be difficult and costly to manufacture.

The VECT-PI project therefore aims to develop new lipids that can better protect mRNA and promote its release inside cells. The researchers also want to understand more precisely how these nanoparticles behave inside cells and how they are distributed throughout the body.

Part of the project will rely on automation and computer models to rapidly test a large number of formulations and identify those that are both the most effective and best tolerated. The new formulations will then be studied in different therapeutic settings, including the treatment of cancers and chronic inflammatory diseases such as psoriasis. The goal is to better tailor lipid nanoparticles to the needs of each therapeutic application while minimizing unwanted effects.

To carry out this project, the consortium brings together complementary expertise in mathematics, computer science, chemistry, physics, and biology, in collaboration with a French platform specializing in mRNA production. By combining these capabilities with the expertise of academic and industrial partners, the project aims to accelerate the development of new mRNA delivery systems and their future use in medicine.