- Department / Institute
- Institut für Schlaganfall und Demenzforschung
- Subject area
- Drug Delivery
- Project title
- Identification of tissue-specific LNPs in cleared mice
- Name of supervisor
- Prof. Dr. Ali Ertürk
- Number of open positions
- Language requirements
- Proficiency in English
- Academic requirements
- Master's Degree
- Project time plan
- Full Doctoral Study-Model: 36 or 48 months
Macromolecular drugs such a DNA, RNA or protein therapeutics promise to revolutionize our ability to treat diseases at the molecular level. However, the efficient and specific delivery of these large biomolecules to specific tissues and cell types is still a largely unsolved problem. Currently, the most promising delivery vehicles are lipid nanoparticles (LNPs), but their ability to specifically deliver drugs to organs other than the liver remains limited1.
Here, we plan to develop methods to accelerate the in vivo testing of LNP formulations in preclinical models to more efficiently find organ and cell type specific delivery vehicles. The method we envisage will be based on the whole-mouse body clearing approaches that are well established in our group2,3. These tissue clearing methods enable the imaging of fluorescently labeled structures at cell-level resolution throughout the whole mouse using light sheet microscopy.
The development of effective delivery platforms will require testing a large number of compounds and combinatorial mixtures of components in vivo, which will be difficult if only a handful of formulations can be tested in a single mouse. Therefore, we plan to combine our tissue clearing methods with molecular barcoding to highly multiplex in vivo screening of LNP formulations.
Promising LNP candidates will be tested individually and further optimized.
The student will develop the whole pipeline from the design and preparation of the LNP and barcode libraries to animal work, imaging and data analysis. In our institute, we value team work and will provide a supportive environment, so that PhD students can build on the expertise that has already been developed in all of the relevant techniques.
1. Yin, H., Kauffman, K. J. & Anderson, D. G. Delivery technologies for genome editing. Nature Reviews Drug Discovery vol. 16 387–399 (2017).
2. Zhao, S. et al. Cellular and Molecular Probing of Intact Human Organs. Cell 180, 796-812.e19 (2020).
3. Cai, R. et al. Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull–meninges connections. Nat. Neurosci. 2018 222 22, 317–327 (2018).