Publication - Abstract
Jun 19, 2019
Dalton Transactions
New supramolecular systems have been prepared by mixing molybdenum organometallic metallosurfactants M(CO)5L and M(CO)4L2 {L = Ph2P(CH2)6<...
Read More
February 16, 2021
RNA-based therapies have great potential to treat many undruggable human diseases. However, their efficacy, in particular for mRNA, remains hampered by poor cellular delivery and limited endosomal escape. Development and optimisation of delivery vectors, such as lipid nanoparticles (LNPs), are impeded by limited screening methods to probe the intracellular processing of LNPs in sufficient detail. We have developed a high-throughput imaging-based endosomal escape assay utilising a Galectin-9 reporter and fluorescently labelled mRNA to probe correlations between nanoparticle-mediated uptake, endosomal escape frequency, and mRNA translation. Furthermore, this assay has been integrated within a screening platform for optimisation of lipid nanoparticle formulations. We show that Galectin-9 recruitment is a robust, quantitative reporter of endosomal escape events induced by different mRNA delivery nanoparticles and small molecules. We identify nanoparticles with superior escape properties and demonstrate cell line variances in endosomal escape response, highlighting the need for fine-tuning of delivery formulations for specific applications.
Publication - Abstract
Jun 19, 2019
Dalton Transactions
Publication - Summary
Apr 27, 2017
Molecular Therapy
The swine influenza pandemic of 2009 and more recent zoonotic transmissions of several avian influenza subtypes to human populations punctuates the threat posed by new pathogens for which we have no pre-existing immunity. Traditional vaccines requi...