DNA barcoded nanoparticles 

How can we make genetic therapies (siRNA, mRNA, CRISPR, etc) safer? We need to deliver them to the right tissue using nanoparticles.

So how do we find nanoparticles that can deliver drugs to a particular tissue? We make thousands of chemically distinct nanoparticles. We have developed screening systems using high throughput microfluidics and DNA barcoding to study how hundreds of LNPs work in a single mouse for the first time. 

How do we test hundreds at once? By 'barcoding' LNPs, and using DNA deep sequencing to measure where they all go at once! For example, the 'heat map' above shows how dozens of LNPs deliver drugs to different cell in vivo - we measured this at all once. We now regularly generate thousands of in vivo drug delivery data points per experiment; this is hundreds of times more in vivo data than a typical experiment. Why is this important? We can study thousands of nanoparticles in vivo to quickly find candidates that deliver genetic drugs to new tissues. ​

High Throughput Screening 
We have developed several barcode screens. Screen one measures nanoparticle distribution (where particles go). Screens 2 and 3 measure where the particles function (which particles deliver mRNA or siRNA that functions in the cell). We can also use barcodes to improve the stability of the drugs themselves.

So what's a typical experiment? We inject ~200 nanoparticles into a mouse, isolate 30 cell types from that mouse, and deep sequence all 30 cell types, thereby generating ~6,000 in vivo data points. We then use custom bioinformatics to analyze which nanoparticle traits (size, composition, etc) affect delivery in vivo. Based  on these bioinformatics data, we make another nanoparticle library.

Once we find a really great nanoparticle, we see how well it functionally delivers siRNA, mRNA, Cas9 mRNA + sgRNA, and / or sgRNA in vivo. Using this approach, we have identified nanoparticles that deliver siRNA, mRNA, Cas9 mRNA + sgRNA, etc., to many different cell types, including non-liver cell types!