Marie Morille: the mega-strategic nanoformulation

When Marie Morille talks about her research into nanovectors and biotherapies, it sounds like something out of science fiction. Injecting microparticles that carry nanoparticles containing messenger RNA around the body... This fundamental research at the Charles Gerhardt Institute (ICGM) is shaping the future of medicine and the formulation of tomorrow's biomedicines. One of her areas of research focuses on the treatment of osteoarthritis using cell therapy. When injected into the joint, stem cells can differentiate into cartilage cells to repair the cartilage. The challenge is therefore to successfully control this differentiation.

How? Thanks to a complex system based on collagen microspheres, which serve both as a support for stem cells and as a reservoir for nanoparticles containing nucleic acids that control differentiation. Her work in this nanometric mechanism involves first developing effective nanovectors to enter cells, then modifying the surfaces of the particles to control their attachment and the timing of the release of these nanosystems. And while proof of concept is in sight, "this research is still very fundamental, "acknowledges the nanoformulations expert.

The new mascot of biomedicine

This work is a logical continuation of his postdoctoral research at the Institute for Regenerative Medicine and Biotherapies (IRMB), which preceded his appointment as a lecturer at the University of Montpellier in 2012. The opportunity to obtain initial results on cartilage repair, as part of a project Inserm Transfertproject. The researcher optimized the formulation of a protein used to promote cell differentiation into cartilage, a result patented in 2012. The conclusive results tested in mice led to an application a few years later by the company Normandie Biotech. "The treatment was used in veterinary medicine for racehorses. It was a pleasant surprise to see such a rapid application," says Marie Morille.

His initial research into nanoparticles dates back to his PhD. His goal at the time was to promote the accumulation of these vectors, used to transport nucleic acids (DNA), in cancer cells, which are the targets of the treatment. "We coat the surface of these nanoparticles with polymers to ensure their stability after intravenous injection. The system is then more likely to accumulate in tumors through an effect known as EPR (enhanced permeability and retention effect), which is based, among other things, on the imperfect nature of the blood vessels supplying the tumors," explains the researcher.

Interest in this mechanism, which was a key focus of her thesis between 2006 and 2009, has since waned. "Although the effects were clearly demonstrated in mice, they were not conclusive in humans,"notes the researcher, who is now working on the new darling of biomedicine: extracellular vesicles (EVs). Secreted by cells, these vesicles are ideal nanovectors for delivering drugs because they are naturally equipped to enter cells. They also show promise for applications in regenerative medicine due to their intrinsic properties, particularly their anti-inflammatory properties. "We just need to figure out how to harness them," says Marie Morille.

Highly competitive sector

His new research project therefore consists of finding a way to stabilize them so that they can be used for treatments. "For example, by modifying the surface of these vesicles with polymer molecules, we are seeking to preserve their physical integrity and biological activity. We have even developed freezing and freeze-drying methods to facilitate their use, and we are currently testing them in collaboration with the Montpellier Cancer Research Institute (IRCM), to track them in the body. We are also interested in their potential for vectorization in another type of biotherapy: intracellular antibodies, also in collaboration with the IRCM," explains the researcher.

Initiated in 2016, this research enabled her to obtain ANR junior funding in 2020 and become an IUF (Institut Universitaire de France) laureate in 2022. This time, with a project on lung treatments. Ve have the advantage of not sticking to mucus, unlike synthetic nanovectors. This property improves the effectiveness of the treatment. "Thanks to a significant reduction in my teaching load, this IUF grant gives me time to work, which is essential because research moves quickly in this highly competitive sector," acknowledges the lecturer, who nevertheless does not forget the teaching component of her work.

California Dreamin'

With two major educational projects: the creation of a platform dedicated to nanoparticles as part of the BioOc program, a project selected in 2022 in response to the call for expressions of interest "Skills and Jobs of the Future " France 2030; and her participation, as co-educational director of the Immune4Cure University Hospital Institute project led by C. Jorgensen. And as if all that weren't enough, Marie Morille is preparing for a year of mobility in September at the University of California Davis in Sacramento.  "This is a pivotal period in my career, very busy but also very exciting," concludes the tireless scientist.