Lipid Nanoparticle Engineering for mRNA-Based Treatment of Male Infertility

Worldwide, 10-15% of couples (or 70 million) face infertility: It is a major public health issue with significant medical, scientific, and economic challenges. Approximately 40% of cases of infertility involve a male factor, and while assisted reproductive technologies can be a solution in some cases, there is no therapeutic solution for males with a genetic cause that results in absence of sperm. With the emergence of nextgeneration sequencing, the identification of genes associated with male infertility is growing rapidly. In project SPERMBACK led by Jessica Escoffier and funded by the (Agence National de Recherche), we aim to develop novel lipid nanoparticles to restore male infertility via mRNA therapy. The aim of this PhD project is: 1. To engineer Lipid Nanoparticles (LNPs) by state-of-the-art techniques such as microfluidics and dual centrifugation. 2. To perform extensive characterization by dynamic light scattering and nuclear magnetic resonance spectroscopy 3. To evaluate LNP efficacies and tolerability in primary cultures of spermatogenic cells. 4. To investigate treatment efficacies ex vivo by quantitative microscopy, confocal microscopy and immunohistochemistry.

The Institute for Advanced Biosciences (IAB) is a joint research center of the Grenoble-Alpes University, the French National Institute of Health and Medical Research (INSERM), as well as the National Center for Scientific Research (CNRS). Within the IAB, the group of Dr. Mans Broekgaarden develops lipid nananomedicines for drug/gene delivery and cancer therapy. In parallel, this work will be performed with the group of Dr. Jessica Escoffier, the lead investigator on this project, whose expertise lies in understanding genetic factors associated to male infertility.

- A solid background in cell biology and nanomedicine/nanobiotechnologies - A strong affinity for cross-disciplinary research on the interface with chemistry, biology, and physics. - Excellent English communication skills, and a collaborative mindset. - Experience in cell culture, Design-of-Experiments (DoE), and or LNP/liposome synthesis will be advantageous