Endogenous non-invasive fluorescence labeling of RNA and its use in cell imaging
RNA is a central molecule of life and has lately emerged as a versatile drug modality. Such RNA-based therapeutics promises a paradigm shift in pharmaceutical research given that the large remaining challenge for this kind of drugs, i.e. their low efficiency of cell delivery, is better understood and eventually solved.
Lipid nanoparticle (LNP) delivery, like in vaccines against SARS-CoV-2, is continuously being optimized and promising delivery vehicles such as extracellular vesicles (EVs) are under development. To facilitate this paradigm shift, I will develop methodologies for non-invasive fluorescence-based microscopy that enable detailed studies of RNA in cells and in drug delivery. Methods for in cellulo non-invasive fluorescence labeling of endogenous RNA are lacking. Using experience from my recent in vitro labeling of mRNA by fluorescent base analogues and serendipitous finding that derivatives of such labels are spontaneously taken up by cells, I will here produce endogenous fluorescent RNA. In this four-year PhD project, I will use this RNA to develop methods for live-cell spatiotemporal monitoring of RNAs. I will also utilize my methods to study RNAs’ EV loading (limiting factor in EV-mediated delivery), trafficking and subsequent uptake in recipient cells. Moreover, I will develop and use parallel, enhanced methods for LNP-mediated RNA delivery. Hence, I will facilitate efforts towards cures against today undruggable diseases and prevention of future pandemics.
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- Swedish Research Council (VR) (Public, Sweden)