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Proefschrift

Investigating lipid formulations for efficient RNA delivery using zebrafish models

Lipid formulations have demonstrated strong potential for nucleic acid delivery,particularly with the success of COVID-19 vaccines. Despite these advances, manyaspects of lipid formulations remain unclear.

Auteur
D. Bi
Datum
11 november 2025
Links
Thesis in Leiden Repository

For instance, how these particles entercells or how their composition might be tuned for targeted delivery to specific tissuesor cell types still needs to be fully understood. This thesis aims to explore theunderlying mechanisms that influence the in vivo behavior of lipid nanoparticles,using zebrafish embryos as a model. Due to their transparency, zebrafish embryosoffer a unique opportunity to observe the dynamic interactions between fluorescentlabelednanoparticles and living cells in real time. They also enable the quantificationof mRNA translation into fluorescent proteins, as well as the effects of gene silencing.Furthermore, by employing CRISPR/Cas9 to generate knockout zebrafish lines, wecan evaluate receptor-specific interactions in a living organism. The overarching aimof this work is to gain mechanistic insight that can inform the design of more effectiveand targeted lipid formulations.

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