# Microfluidic Device Type Improves Heart mRNA Delivery In Vivo

## TL;DR

Changing how lipid nanoparticles are made can significantly improve mRNA delivery to the heart in mice.

## Contribution

A new method using a herringbone mixer improves heart-targeted mRNA delivery compared to traditional mixing.

## Key findings

- LNPs made with a herringbone mixer delivered twice as much mRNA to the heart as those made with a bifurcating mixer.
- Improved delivery was linked to differences in protein corona adsorption and systemic physiology.
- Spatial transcriptomics confirmed mRNA delivery to diseased heart regions and cardiomyocytes in a mouse model.

## Abstract

To improve lipid nanoparticle (LNP)-mediated delivery
to nonliver
tissues, scientists modify LNP chemistry or add targeting ligands.
One underexplored alternative is to change the formulation process
that creates the LNP. Here, we report that an LNP formulated with
a herringbone mixer led to 2-fold more heart delivery than the same
LNP formulated with a bifurcating mixer. The two LNPs had similar
biophysical traits, yet they adsorbed different protein coronas, suggesting
that the effect was driven by systemic physiology. By using spatial
transcriptomics to track LNP delivery in a mouse model of atherosclerosis,
we found that the improved LNP delivered mRNA to diseased regions
and cardiomyocytes after an intravenous injection. These data suggest
that it is possible to increase heart delivery via nanoparticle processing.