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To the Lung and Beyond

mRNA technology has proven its immense utility in combating the COVID-19 pandemic. The heightened interest in mRNA technology has opened up new avenues to showcase its significant potential. Scientists are now more than ever seamlessly working on developing new vaccines and therapeutic designs using mRNA.

A crucial aspect of mRNA technology lies in the effective delivery of nucleic acids. While there are various new methods and traditional approaches such as liposomes, the preferred method, as demonstrated in FDA-approved COVID vaccines, involves lipid nanoparticle (LNP) delivery.

LNPs are not magical delivery systems, and without specific design, extrahepatic mRNA delivery remains elusive. Finding the best extrahepatic mRNA delivery agents through in vivo studies with a library of designs sacrifices a substantial number of lab animals and can only cover a fraction. Additionally, in vitro studies do not resonate well with in vivo studies, making in vivo studies the primary method for assessing delivery efficacy.

To address this challenge, a recent study in Nature Communications describes an alternative high-throughput approach where barcoded DNA-based LNP system is in play. This allows for the simultaneous exposure of lab animals to various cationic degradable LNPs. Ninety-six out of 180 cationic degradable (CAD) LNPs, each carrying mRNA encoding firefly luciferase (Fluc) and b-DNA, were systematically administered to a pool of mice. DNA sequencing analysis identified 21 promising CAD LNPs for pulmonary delivery. The best performing CAD LNP was identified through Fluc mRNA delivery preferentially to lungs in mice, where roughly 90 % of the total luminescence flux was observed. This same LNP exhibited optimal performance across various mRNA payloads, demonstrating significant therapeutic potential.

This proof of principle study clearly demonstrates a promising high-throughput methodology for screening various LNP designs in the quest to identify the best candidates for therapeutic applications.

To read further on the study, please refer to the following link:

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