RNA-mediated local immunomodulation using nanomedicine for the treatment of inflammatory bowel disease

The objective of this thesis project is to design and characterize RNA-loaded lipid nanoparticles (LNPs) for oral administration. These LNPs, engineered for enhanced stability, will enable targeted delivery and localized drug release in inflamed areas of the intestine. A comprehensive physicochemical characterization of the nanoparticles will be performed, along with in vivo studies to assess their biodistribution and therapeutic efficacy.

Activities:

• The student will formulate customized RNA-loaded lipid nanoparticles using a microfluidic approach and characterize them through various techniques, including DLS, HPLC-UV, A4F, electrophoresis, NTA, and CryoTEM.

• The student will assess both RNA stability and LNP stability in different biological media relevant for the project.

• Additionally, the student will conduct in vivo studies to evaluate the biodistribution and therapeutic efficacy of the nanoparticles in various mouse models of inflammatory bowel diseases.

Skills and competences to be acquired:

Firstly, the student will learn the importance of bibliographic research, which will be integrated with daily practical work in the laboratory. Key skills to be developed will include organization and the ability to draft reports and protocols to track laboratory activities. Additionally, the student will acquire strong presentation skills, particularly in front of a diverse audience. The student is also expected to contribute to national and international conferences on nanotechnology and write high-quality scientific papers.

The student will gain transdisciplinary knowledge in the preparation of RNA-loaded nanoparticles, their physicochemical characterization, and their application in oral drug delivery. He/She will learn to operate instruments dedicated to the production of nanoparticles through microfluidics, as well as techniques for the physicochemical characterization of nanosystems. Additionally, the student will evaluate the efficacy of these systems at the pre-clinical level, as outlined in the planned activities. He/She will participate in collective laboratory tasks and contribute to the scientific and collaborative activities of the group.

Application:

Candidates should send a Cover Letter, a CV, recommendation letters, and grade transcripts, by email to:

Giovanna LOLLO: giovanna.lollo@univ-lyon1.fr

David KRYZA: david.kryza@univ-lyon1.fr